Molecular Syndromology[JOURNAL]
Sun
200 papers
Two Moroccan Families with Emery-Dreifuss Muscular Dystrophy and Report of a Novel Pathogenic Variant.
Rahmuni Y, El Kadiri Y, Lyahyai J … +4 more , Birouk N, Nesnassi M, Sefiani A, Ratbi I
Mol Syndromol · 2024 Dec · PMID 39634247 · Full text
BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder characterized by muscle weakness and atrophy associated with early tendon retractions and late cardiomyopathy. Among several genes, and a...
BACKGROUND: Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder characterized by muscle weakness and atrophy associated with early tendon retractions and late cardiomyopathy. Among several genes, and are the major ones (55%). Due to intra- and inter-familial heterogeneity, only NGS allows to confirm with certainty EDMD by identifying the mutation in the causal gene. CASE PRESENTATION: We report clinical and molecular data of two unrelated Moroccan patients with EDMD in whom we identified a deleterious hemizygous splicing variant NM_000117.3(): c.399 + 1G>T and a novel frameshift variant NM_170707.4(): c.1549_1550delCA, respectively. Carrier status of the variant was investigated in several relatives at risk. CONCLUSION: We emphasize the importance of NGS as a powerful genetic tool in EDMD for accurate molecular diagnosis, effective clinical management of patients, and appropriate genetic counseling of families.
Screening for Variants in Egyptian Patients with Pontocerebellar Malformations.
Emam BA, Abdel-Hamid MS, Eid M … +6 more , Girgis M, Ragab OA, Zaki MS, El-Kiki H, Abdel-Hady S, Abdel-Salam GMH
Mol Syndromol · 2024 Dec · PMID 39634246 · Full text
INTRODUCTION: Pontocerebellar hypoplasia (PCH) represents a group of rare disorders with prenatal onset and time-dependent loss of brain parenchyma, predominantly affecting the cerebellum and pons with variable involveme...
INTRODUCTION: Pontocerebellar hypoplasia (PCH) represents a group of rare disorders with prenatal onset and time-dependent loss of brain parenchyma, predominantly affecting the cerebellum and pons with variable involvement of supratentorial structures. Radiologically and pathologically, they are characterized by small cerebellum and pons. Our study aimed to screen for the gene variants in Egyptian patients with PCH for proper counseling and to describe the brain MRI and the clinical phenotype and compare, them to those described in the literature. METHODS: Thirty patients from thirty Egyptian families with a diagnosis of PCH based on neuroimaging findings were selected. Clinical evaluation, radiological findings, and genetic investigations were done for all patients. RESULTS: The common missense variant c.919G>T (p.A307S) was identified in only 6 patients from six unrelated families (6/30; 20%) who showed different degrees of pontocerebellar malformations on brain imaging. CONCLUSION: The presence of a dragonfly/butterfly-like pattern in the coronal section of the cerebellum recommends genetic testing of as a first step. For negative cases, whole-exome sequencing is essential to reach a definite diagnosis and determine the etiology.
Mitochondrial DNA Depletion Syndromes Gene Panel versus Clinical Exome Sequencing in Children with Suspected Mitochondrial Hepatopathies.
Doğulu N, Köse E, Ceylaner S … +4 more , Kasapkara ÇS, Bozaci AE, Oncul U, Eminoğlu FT
Mol Syndromol · 2024 Dec · PMID 39634245 · Full text
INTRODUCTION: Mitochondrial DNA depletion syndromes (MDDSs) are a group of clinically and genetically heterogeneous disorders. In the present study, we aimed to investigate the frequency of MDDS in children under the age...
INTRODUCTION: Mitochondrial DNA depletion syndromes (MDDSs) are a group of clinically and genetically heterogeneous disorders. In the present study, we aimed to investigate the frequency of MDDS in children under the age of 5 years with suspected mitochondrial hepatopathy and to evaluate this group of patients using MDDS gene panel and clinical exome sequencing (CES) genetic analysis methods. METHODS: Patients under 5 years of age who were clinically suspected to have mitochondrial hepatopathy and had neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset were included. RESULTS: Forty patients (20 female, 50%) were enrolled, with a median age of 102 [57-263.8] days. Icteric appearance was identified in 28 (70%) of the patients, hepatomegaly in 27 (67.5%), splenomegaly in 10 (25.0%), and hypotonicity in 10 (25.0%); moreover, elevated international normalized ratio was detected in 77.5%, cholestasis in 77.5%, and elevated lactate levels in 62.5%. Molecular genetic diagnosis was made in 9 patients (22.5%) with the MDDS gene panel and in 17 (42.5%) patients with the CES analysis. All patients diagnosed with MDDS had a history of parental consanguinity, while the rate in those without MDDS was 54.8% ( = 0.012). High lactate levels were identified in all those with MDDS, but in only 51.6% of those without MDDS ( = 0.020). CONCLUSION: Present study revealed that demographic findings and laboratory assessments are insufficient to diagnose genetically inherited diseases in children presenting with hepatic involvement. While one-fifth of the patients with suspected mitochondrial hepatopathies were diagnosed with MDDS, it is revealed that around half of patients can be diagnosed with CES panel.
Whole Exome Sequencing of a Multiplex Family of Indian Origin Identifies Variants in the and Genes within the 17p11.2 Region in Siblings with Autism and Smith Magenis Syndrome.
Srividhya D, Parambath SV, Sathyanarayanan R … +6 more , Huligerepura Sosalegowda A, Korlimarla A, Niranjana Murthy AS, Prabhakaran N, Vijayanand M, Gowda NKC
Mol Syndromol · 2024 Dec · PMID 39634244 · Full text
INTRODUCTION: Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by restrictive repetitive behavior and impairment in social and communication skills. They are extremely heterogeneous...
INTRODUCTION: Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by restrictive repetitive behavior and impairment in social and communication skills. They are extremely heterogeneous with a strong genetic preponderance. They are clinically highly convoluted, presenting with multiple comorbid conditions and syndromic features. More than 100 genes have been identified to date. METHOD: Whole exome sequencing (WES) has emerged as a valuable tool in evaluating the genetic underpinnings of ASDs, be it the syndromic or the idiopathic variants. In the current study, we performed WES on a multiplex family of Indian origin to investigate the disease etiology in the siblings (S1 [Female] and S2 [Male]) exhibiting ASD syndromic features, at both clinical and genetic aspects. RESULTS: Exome sequencing identified a missense variant (NM_030665.4:c.5320C>T; p.Arg1774Trp) in S1 resulting in haploinsufficiency. Validation by Sanger sequencing confirmed that the variant was true positive and maternally transmitted in the subject. Likewise, we report an inherited missense variant at the same locus (17p11.2) corresponding to the (NM_002018.4:c.2030A>C; p.Glu677Ala) in the other sibling, S2. Both the variants were reported in the Smith Magenis syndrome (SMS) critical region justifying their contribution to the presentation of the syndromic SMS features. These WES findings were consistent with the clinical findings that imply SMS features in both siblings. CONCLUSION: The current study employed WES to provide insights into the genetic complexity associated with syndromic ASD and how that contributes to the disease heterogeneity. Moving forward, combinatorial approaches and findings from syndromic ASDs can potentially act as indicators to understand the genetic and phenotypic variations seen in idiopathic ASD.
Microdeletion 3q13.2q21.2 in a Patient Previously Diagnosed with MOMO Syndrome.
de Oliveira-Sobrinho RP, Rare Genomes Project Consortium, Vieira TP … +1 more , Steiner CE
Mol Syndromol · 2024 Dec · PMID 39634243 · Full text
BACKGROUND: MOMO syndrome is a rare disorder with variable presentation and unknown etiology belonging to the overgrowth syndromes group. CASE PRESENTATION: The authors describe a patient presenting with severe developme...
BACKGROUND: MOMO syndrome is a rare disorder with variable presentation and unknown etiology belonging to the overgrowth syndromes group. CASE PRESENTATION: The authors describe a patient presenting with severe developmental delay, absent speech, autism spectrum disorder, central nervous system malformations, bilateral optic atrophy, and postnatal overgrowth, besides a dysmorphic and progressive coarse face. A clinical diagnosis of MOMO syndrome was proposed, but he developed megaesophagus, megacolon, paraparesis, and severe acne during the clinical follow-up, which are not described in this condition. Whole-genome sequencing detected a deletion of 11.9 Mb at 3q13.2q21.2 comprising 80 genes, including the gene associated with Primrose syndrome. CONCLUSION: Despite the atypical manifestations in this patient, the overlapping features between MOMO syndrome, Primrose syndrome, and 3q13.31 deletion led the authors to propose that MOMO syndrome could be part of the Primrose/3q13.31 microdeletion syndrome spectrum.
Erratum.
Mol Syndromol · 2024 Dec · PMID 39634242 · Full text
[This corrects the article DOI: 10.1159/000539115.].
[This corrects the article DOI: 10.1159/000539115.].
Two-Compound Heterozygous Deletions Affecting in a Patient with Microcephaly and Ocular Abnormalities and in an Unborn Sibling with Abnormal Sulcation.
Pal S, Kulshrestha S, Garg N … +3 more , Gupta D, Gupta ND, Puri RD
Mol Syndromol · 2024 Dec · PMID 39634241 · Full text
INTRODUCTION: -related disorder is a known cause of autosomal recessive microcephaly and chorioretinopathy, which was originally recognized as a new syndrome based on unique ocular findings on a phenotypic overlap of mic...
INTRODUCTION: -related disorder is a known cause of autosomal recessive microcephaly and chorioretinopathy, which was originally recognized as a new syndrome based on unique ocular findings on a phenotypic overlap of microcephalic primordial short stature. Since the elucidation of its molecular mechanism, limited families have been published in literature and the disorder remains rare worldwide. CASE PRESENTATION: We present the first Indian family with an affected child and sibling fetus with microcephaly, dysmorphism, and agyria/pachygyria complex on brain imaging in both and short stature, intellectual disability, and visual impairment in proband. As for many patients with long diagnostic odysseys, this child also underwent multiple genomic tests. Genome sequencing through the Indian Undiagnosed Disease Program (I-UDP) confirmed the diagnosis in both proband and sibling fetus. Compound heterozygous variants were identified in including an eleven base pair deletion (inherited from father) and 405 base pair large deletion (inherited from mother). Reverse phenotyping to confirm the ocular phenotype in proband confirmed -related microcephaly and chorioretinopathy. We report third trimester microcephaly with ventriculomegaly and abnormal sulcation as part of the antenatal presentation for this condition. CONCLUSION: This case represents an Indian family with a seemingly obvious clinical diagnosis compounded by a long diagnostic odyssey and the first ever structural variant to be identified via whole genome sequencing in in trans with an indel variant.
Dysmorphic Findings in SAHH Deficiency with a Novel Variant in the Gene.
Ciki K, Alavanda C
Mol Syndromol · 2024 Dec · PMID 39634240 · Full text
INTRODUCTION: S-adenosylhomocysteine hydrolase (SAHH) is one of the enzymes involved in converting methionine to homocysteine with transmethylation processes. Methyltransfer reactions are impaired in SAHH deficiency. SAH...
INTRODUCTION: S-adenosylhomocysteine hydrolase (SAHH) is one of the enzymes involved in converting methionine to homocysteine with transmethylation processes. Methyltransfer reactions are impaired in SAHH deficiency. SAHH deficiency is multisystemic and antenatal onset disorder. It is also ultra rare disease. Only 19 cases have been reported so far. CASE PRESENTATION: We report an eighteen-month-old female patient who was investigated due to elevated transaminase levels, coagulopathy, cataract, hypotonia, and global developmental delay. She also had dysmorphic findings. Significant methionine elevation and mild homocysteine elevation were detected. Other metabolic investigations and laboratory findings were unremarkable. Homozygous novel variant in the gene and heterozygous novel variant in the gene were found by whole-exome sequencing (WES) analysis. Methionine restricted diet, phosphatidylcholine, and creatine supplements were advised. CONCLUSION: In this report, a case with a novel variant in the gene and prominent dysmorphic findings was reported. More SAHH deficiency cases with different findings and phenotypes will be revealed through the use of WES and genetic panels.
A Novel Variant in an Asymptomatic Adolescent Girl with Progressive Cavitating Leukoencephalopathy.
Caliskan E, Sager SG, Ayaz A … +2 more , Teralı K, Gunbey HP
Mol Syndromol · 2024 Dec · PMID 39634239 · Full text
INTRODUCTION: Pathogenic variants in several genes encoding components of the mitochondrial respiratory chain have been linked to various clinical phenotypes such as progressive cavitating leukoencephalopathy (PCL). The...
INTRODUCTION: Pathogenic variants in several genes encoding components of the mitochondrial respiratory chain have been linked to various clinical phenotypes such as progressive cavitating leukoencephalopathy (PCL). The association between PCL, previously linked to numerous gene mutations in the literature, and the gene mutations has emerged as a recent and noteworthy discovery. PCL is generally diagnosed in symptomatic patients during the early years of life, mostly in infancy. CASE PRESENTATION: In a previously healthy 12-year-old Turkish girl, a computed tomography scan taken for minor head trauma incidentally revealed suspicious hypodense areas in the periventricular white matter. Subsequently, a magnetic resonance imaging evaluation was performed. There was no history of motor regression, irritability, or seizures up to the age of 12. The case exhibited normal neurological and cranial nerve examinations. Magnetic resonance imaging detected bilateral periventricular T2/FLAIR hyperintensities with cystic areas suggestive of PCL. Whole-exome sequencing revealed the presence of a homozygous p.R222C missense variant in the gene. Over a 6-year follow-up period, the patient remained asymptomatic, and there were no discernible changes in the magnetic resonance imaging findings. CONCLUSION: This case underscores the association between a potentially causal variant at the locus and PCL. It is worth noting that this novel variation in PCL can not only manifest with symptoms in the infantile period but also remain asymptomatic into adolescence.
Investigation of Genetic Changes in Three Families with Bipolar Disease.
Çolak-Geniş E, Özdemir Erdoğan M, Çam FS … +4 more , Aydemir Ö, Akin F, Gerik-Celebi HB, Solak M
Mol Syndromol · 2024 Dec · PMID 39634238 · Full text
INTRODUCTION: Bipolar disorder (BD) is a serious psychiatric disorder characterized by mood swings (depressive and manic phases) that can strongly affect the quality of life of patients and their families. The lifetime p...
INTRODUCTION: Bipolar disorder (BD) is a serious psychiatric disorder characterized by mood swings (depressive and manic phases) that can strongly affect the quality of life of patients and their families. The lifetime prevalence of BD in the general population is 1%. The pathogenesis of BD is unknown; however, comprehensive epidemiological studies have shown that both genetic and environmental factors play a role. Within the scope of the current project, we aim to determine the genetic change responsible for the emergence of the disease and to make a genotype-phenotype correlation. METHODS: In this study, we evaluated single nucleotide gene variants in three families ( = 6 patients) with bipolar disorder using whole-exome sequencing. RESULTS: Seven genes (, , , , , , and ) were identified as possibly associated with BPD. In addition, two novel variants were presented in the (c.1214T>G) and (c.8288C>G) genes. CONCLUSION: Prospective studies in larger patient groups are required to determine the role of these genes in the etiology of the disease and their potential in diagnosis and treatment. To the best of our knowledge, this is the first methodically comprehensive study conducted in our country and can contribute to the identification of genes that may be associated with BD and the etiopathogenesis of the disease.
Novel Splice Site Pathogenic Variant in STXBP1 Gene in a Child with Intellectual Disability, Epilepsy, and Autism Spectrum Disorder: A Case Report.
Amllal N, Lyahyai J, Elalaoui SC … +2 more , El Kadiri Y, Sefiani A
Mol Syndromol · 2024 Oct · PMID 39359953 · Full text
INTRODUCTION: Pathogenic variants in the gene are associated to a large spectrum of severe early onset developmental and epileptic encephalopathies (OMIM #612164). They were also identified in various other neurodevelop...
INTRODUCTION: Pathogenic variants in the gene are associated to a large spectrum of severe early onset developmental and epileptic encephalopathies (OMIM #612164). They were also identified in various other neurodevelopmental disorders. This gene encodes for the syntaxin-binding protein 1, a member of the SEC-1 family of membrane-transport proteins that modulate the presynaptic vesicular fusion by interacting with soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). However, the physiopathology of pathogenic variants is not yet fully understood. CASE PRESENTATION: Herein, we report a patient presenting intellectual disability, early onset seizures, and autism. Clinical exome sequencing identified a novel monoallelic splice pathogenic variant (NM_001032221.6):c.38-2A>G. DISCUSSION: Splice-site pathogenic variants in the gene are mostly associated with West syndrome, early onset epilepsy and encephalopathy, and Ohtahara syndrome. Our findings extend clinical and molecular spectrum of gene variants by reporting the first splice-site variant associated with autism along with early onset epilepsy and, and intellectual disability in a patient.
Atlantoaxial Instability due to Os Odontoideum in a Child with Christianson Syndrome.
Güven NE, Uçmak H, İlter Uçar Ç … +4 more , Havan M, Yıldırım M, Teber S, Kendirli T
Mol Syndromol · 2024 Oct · PMID 39359952 · Full text
INTRODUCTION: Christianson syndrome is a rare neurodevelopmental disorder associated with mutations in the gene located on the chromosome X. It is characterized by intellectual disability, developmental delay, speech an...
INTRODUCTION: Christianson syndrome is a rare neurodevelopmental disorder associated with mutations in the gene located on the chromosome X. It is characterized by intellectual disability, developmental delay, speech and language impairments, dysmorphic features, seizures, ataxia, and neurobehavioral problems. CASE PRESENTATION: A 5-year-old boy was presented with respiratory failure and then progressive muscle weakness in all four extremities. He manifested acquired microcephaly, intellectual disability, global developmental delay, distinct dysmorphic facial features, seizures, spastic tetraparesis, truncal hypotonia, speech impairment, failure to thrive, malnutrition, recurrent lung infections, self-mutilation, primary hyperparathyroidism, medullary nephrocalcinosis, and atlantoaxial instability due to os odontoideum. Brain magnetic resonance imaging revealed atlantoaxial instability due to os odontoideum, a narrow foramen magnum, myelopathy due to spinal cord compression, and cerebral and cerebellar atrophy. DISCUSSION: This report highlights a significant contribution by introducing a child with Christianson syndrome describing atlantoaxial instability due to os odontoideum, a previously undocumented phenomenon. This report suggests a potential link between Christianson syndrome and atlantoaxial instability. In children with Christianson syndrome experiencing increased muscle weakness in all extremities during follow-up, consideration of underlying myelopathy due to os odontoideum is advised.
A Recurrent c.416C>T Variant in the B3GAT3 Gene in the Turkish Population: Report of Two Siblings and Expanding the Clinical Spectrum.
Daşar T, Kolkıran A, Sezer A … +2 more , Bal E, Kılıç E
Mol Syndromol · 2024 Oct · PMID 39359951 · Full text
INTRODUCTION: Linkeropathies are a group of rare multi-systemic genetic disorders primarily affecting the skeletal and cardiac systems due to defects in the enzymes responsible for proteoglycan synthesis. CASE PRESENTATI...
INTRODUCTION: Linkeropathies are a group of rare multi-systemic genetic disorders primarily affecting the skeletal and cardiac systems due to defects in the enzymes responsible for proteoglycan synthesis. CASE PRESENTATION: We present a case of two siblings with the B3GAT3 variant. The 14-year-old boy exhibited short stature, severe kyphoscoliosis, splenomegaly, and aortic root dilatation, along with several physical abnormalities including bifid uvula, blue sclera, limited elbow extension, and pectus carinatum. His 6-year-old sister also exhibited comparable yet less pronounced physical features. Clinical exome sequencing analysis revealed a homozygous c.416C>T variant in the B3GAT3 gene for the sister; the same variant was also present in the boy patient. The boy underwent preoperative halo-gravity traction for severe kyphoscoliosis, followed by posterior instrumentation and fusion surgery without complications. DISCUSSION/CONCLUSION: B3GAT3-related linkeropathy syndrome is a rare disorder and we further expand the clinical spectrum with novel findings.
Biallelic Deletion of Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.
Yalçınkaya B, Sağlam KA, Terali K … +3 more , Tekin E, Taslak H, Türkyılmaz A
Mol Syndromol · 2024 Oct · PMID 39359950 · Full text
INTRODUCTION: Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infant...
INTRODUCTION: Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD), rhizomelic chondrodysplasia punctata type 1, and Heimler syndrome. PBD phenotypes manifest through hypotonia, developmental delay, facial dysmorphism, seizures, liver dysfunction, sensorineural hearing loss, and retinal dystrophy. METHODS: The proband underwent comprehensive clinical evaluation, followed by whole-exome sequencing (WES) coupled with copy number analysis (CNV), aimed at identifying potential disease-causing variants aligning with the observed phenotype. RESULTS: Our findings detail an individual exhibiting developmental delay, hearing loss, visual impairment, hepatomegaly, and splenomegaly, attributed to a biallelic deletion of exon 4 in the gene. The WES analysis of the index case did not uncover any pathogenic/likely pathogenic single-nucleotide variations that could account for the observed clinical findings. However, the CNV data derived from WES revealed a homozygous deletion in exon 4 of the gene (NM_001127649.3), providing a plausible explanation for the patient's clinical features. The exon 4 region of encodes the transmembrane domain of the protein. The transmembrane domain plays a crucial role in anchoring the protein within lipid bilayers, and its absence can disrupt proper localization and functioning. As a result, this structural alteration may impact the protein's ability to facilitate essential cellular processes related to peroxisome biogenesis and function. CONCLUSION: The index patient, which presented with hearing loss, retinal involvement and hepatic dysfunction in adolescence age, has atypical clinical course that can be considered unusual for Zellweger syndrome (ZS) and IRD phenotypes, and its rare genotypic data (in-frame single exon deletion) expands the PBD disease spectrum. This study revealed for the first time that PEX26 protein transmembrane domain loss exhibits an unusual course with clinical findings of IRD and ZS phenotypes. WES studies, incorporating CNV analyses, empower the identification of novel genetic alterations in genes seldom associated with gross deletion/duplication variations, such as those in the gene. This not only enhances diagnostic rates in rare diseases but also contributes to broadening the spectrum of causal mutations.
A 37-kb Deletion in Region 16p13.3 in an Infant with Osteopetrosis and Congenital Diarrhea Including the CLCN7 and PERCC1 Genes.
Sandal S, Kayhan G, Kahvecioglu D … +8 more , Vezir E, Kilic A, Köse A, Tas Ersun M, Derme T, Bahap Y, Dereci S, Hizli S
Mol Syndromol · 2024 Oct · PMID 39359949 · Full text
INTRODUCTION: Congenital diarrhea presents a diagnostic challenge in cases where standard assessments are inconclusive. CASE PRESENTATION: We report a female infant with thrombocytopenia, increased bone density, and pale...
INTRODUCTION: Congenital diarrhea presents a diagnostic challenge in cases where standard assessments are inconclusive. CASE PRESENTATION: We report a female infant with thrombocytopenia, increased bone density, and pale optic disc symptoms, suggestive of osteopetrosis. However, she also exhibited noninfectious, blood- and mucus-free diarrhea, not accounted for by osteopetrosis. Genetic testing, including clinical exome sequencing and chromosomal microarray analysis, revealed a homozygous 39-kb deletion on chromosome 16p13.3. This deletion spanned the gene associated with osteopetrosis and the gene implicated in congenital diarrhea. CONCLUSION: This case illustrates the importance of considering 16p13.3 deletions when confronted with the dual presentation of congenital diarrhea and osteopetrosis, expanding the diagnostic considerations for similar clinical presentations.
Determination of the Frequency of BCL-2 Polymorphisms (c.-717C>A and c.*2364G>A) and LIF Polymorphism (c.*1414T>G) in Patients with Congenital Anomalies of the Kidney and Urinary Tract.
Oztepe T, Sahin FI, Yilmaz AC … +3 more , Baskin E, Haberal M, Terzi YK
Mol Syndromol · 2024 Oct · PMID 39359948 · Full text
INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are characterized by several malformations. Its prevalence is 0.3-0.6% in live births. The B-cell lymphoma () gene regulates apoptosis, and the L...
INTRODUCTION: Congenital anomalies of the kidney and urinary tract (CAKUT) are characterized by several malformations. Its prevalence is 0.3-0.6% in live births. The B-cell lymphoma () gene regulates apoptosis, and the Leukemia Inhibitory Factor () gene plays a role in many biological processes, such as blastocyst growth and uterine preparation for implantation. In this study, two single nucleotide polymorphisms (SNPs) of the gene (rs2279115 and rs4987856) and one SNP of the gene (rs929271) were investigated in CAKUT patients for the first time. METHODS: Hundred and twenty-nine CAKUT patients and 105 controls were enrolled in this study. We used polymerase chain reaction-restriction fragment length polymorphism for rs2279115 and rs929271 and SNaPshot for rs4987856. The χ test was used to compare discrete variables, and the independent sample test was used to compare continuous variables. RESULTS: The allele frequencies for the rs2279115 and rs4987856 polymorphisms of and the rs929271 polymorphism of were not significantly different between the patient and control groups ( = 0.162, = 0.053, = 0.635, respectively). However, the co-segregation analysis revealed a significant difference in the distribution of allele frequencies between the patient and control groups for two genetic variations: rs929271 SNP and rs4987856 SNP ( = 0.034). The relative odds ratio was 2.444 (95% Confidence Interval (CI) 1.054-5.671). CONCLUSION: This study, which is the first time in the literature, showed that changes in and genes are associated with CAKUT disease.
-Related Neurodevelopmental Disorder Is Clinically Recognizable.
Prasun P, Patra K
Mol Syndromol · 2024 Oct · PMID 39359947 · Full text
INTRODUCTION: encodes eukaryotic elongation factor 2 which catalyzes the elongation phase of protein translation. It is ubiquitously expressed and important for neuronal function. was first associated with adult-onset...
INTRODUCTION: encodes eukaryotic elongation factor 2 which catalyzes the elongation phase of protein translation. It is ubiquitously expressed and important for neuronal function. was first associated with adult-onset spinocerebellar ataxia type 26 (SCA26). A novel neurodevelopmental disorder associated with de novo heterozygous variants in has been described. Only 6 patients have been described in the literature thus far. A 9-year-old child with de novo novel missense variant is described here. -related neurodevelopmental disorder appears to be clinically recognizable. CASE PRESENTATION: A nine-year-old male with autism spectrum disorder was referred for genetic evaluation. On examination, he had relative macrocephaly and frontal prominence. Whole exome sequencing revealed a de novo c.1225 C>T: p. (R409W) variant in exon 9 of the gene (NM_001961.3). DISCUSSION: A comparison of clinical findings suggests that relative macrocephaly/macrocephaly and prominent forehead are consistent and easily identifiable clinical features of -related neurodevelopmental disorder. The clinical spectrum of this disorder is still emerging. -related neurodevelopmental disorder should be considered in a child with autism, developmental delays/intellectual disability, macrocephaly/relative macrocephaly, and frontal prominence.
Deletions Identified by Genome Sequencing in Two Individuals with Xia-Gibbs Syndrome.
Bertrand M, Shah G, Pedersen BS … +8 more , Schulz A, Weise A, Liehr T, Huppke P, DiTroia S, Quinlan AR, Haack TB, Husain RA
Mol Syndromol · 2024 Oct · PMID 39359946 · Full text
INTRODUCTION: Xia-Gibbs syndrome (XGS) is a rare syndromic disorder characterized by developmental delay with intellectual disability, muscular hypotonia, brain anomalies, and nonspecific dysmorphic features. Different h...
INTRODUCTION: Xia-Gibbs syndrome (XGS) is a rare syndromic disorder characterized by developmental delay with intellectual disability, muscular hypotonia, brain anomalies, and nonspecific dysmorphic features. Different heterozygous variants in have been reported as causal for XGS, comprising mainly stop-gain and frameshift events, but also missense variants, deletions, and a duplication of the locus. CASE PRESENTATION: We hereby report 2 patients with clinical features of XGS. In the first patient, a interstitial deletion in 1p36.11p35.3 encompassing the entire coding region of was initially suspected by trio exome sequencing and subsequently confirmed by shallow genome sequencing. In the second patient, a deletion comprising most of the 5' untranslated region of was detected by genome sequencing. CONCLUSION: We identified the smallest deletion comprising reported so far by shallow genome sequencing as well as another small deletion by genome sequencing. These methods represent useful techniques for the identification and confirmation of small deletions and structural variants. Furthermore, our data provide additional evidence of haploinsufficiency as a disease mechanism in XGS. Clinically, foot deformity, skin and connective tissue abnormalities observed in one of the patients are consistent with other reported cases of XGS. These findings suggest that these manifestations could be considered as more prevalent characteristics, underscoring the importance of in-depth phenotyping.
A Novel Missense Variant in the Underlies Spondyloepiphyseal Dysplasia with Congenital Joint Dislocations.
Mughal TA, Asim M, Gillani SHUH … +5 more , Chughtai NO, Batool SA, Hussain A, Shujaat K, Gilani SZT
Mol Syndromol · 2024 Oct · PMID 39359945 · Full text
BACKGROUND: Spondyloepiphyseal dysplasia (SED) is characterized by skeletal dysplasia and multiple joint dislocations. SEDs encompass various types, such as SED congenita, SED tarda (SED-T), SED with congenital joint dis...
BACKGROUND: Spondyloepiphyseal dysplasia (SED) is characterized by skeletal dysplasia and multiple joint dislocations. SEDs encompass various types, such as SED congenita, SED tarda (SED-T), SED with congenital joint dislocations (SED-CJD), SED stanescu, and SED-T with progressive arthropathy. METHODS AND RESULTS: In the present study, we clinically and genetically characterized a consanguineous Pakistani family with SED-CJD. The affected member showed large joint dislocation, spinal deformities, and previously unreported facial features. Exome sequencing followed by Sanger sequencing revealed a missense variant, [c.601T>A; p.(Tyr201Asn)], in the . CONCLUSION: This study has not only expended the mutation spectrum in the gene but also will facilitate diagnosis and genetic counseling of related features in the Pakistani population.
Distinct Distribution of HBB Variants in Two Cohorts of Beta Thalassemia Patients, and a Novel Variant from Turkey.
Kocak Eker H, Balasar O
Mol Syndromol · 2024 Oct · PMID 39359944 · Full text
INTRODUCTION: Beta thalassemia is a serious disease for which mutation-based diagnostic and screening tests are readily available. These tests are based on specific variant profile in the regions of the testing centers....
INTRODUCTION: Beta thalassemia is a serious disease for which mutation-based diagnostic and screening tests are readily available. These tests are based on specific variant profile in the regions of the testing centers. De novo mutations and migration change the distribution of these variants. We aim to update the variant spectrum in the gene in our region. In addition, we present a variant, which not been detected before in Turkey, and also a changed classification of another variant. METHODS: This study includes 142 patients (46 of Turkish, 96 of Syrian) who were investigated for defects in their β-globin gene with Sanger sequencing. Clinically, 52 of these patients had thalassemia major, and 90 had thalassemia minor. RESULTS: Twenty three types of pathogenic variants were identified causing beta thalassemia and abnormal hemoglobins. Variant distribution has differed considerably between Turkish and Syrian patients. While the IVSI-110G>A was the most prevalent variant (41.1%) in Turkish patients, the IVSII-1G>A and Codon 39 (C>T) variants were found in 22% and 21.3%, respectively, in Syrian patients. We detected the novel c.31_32insT variant in 3 Syrian patients. CONCLUSION: The detection of updated regional variant spectrum will contribute to future prenatal and/or postnatal molecular diagnostic tests. Also, our study presents a novel variant that was not previously reported.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe