Durmaz B, Karaca E, Tavmergen Goker EN
… +6 more, Tavmergen E, Sahin G, Akdogan A, Yasar BP, Gunduz C, Ozkinay R
Genet Couns
· 2016 · PMID 30226964
The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in d...The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in different aspects. PGS was performed in a total of 84 couples (87 cycles) between the period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18, 21, 22, X and Y depending on the indication. The diagnostic and clinical data were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety-eight of them were found to be suitable for transfer. They were transferred to 72 patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most common indication was unexplained infertility. The implantation rate was calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The highest rate of healthy living births is achieved in patients having low grade maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had normal chromosomal structure which we can propose it as an alternative test for couples at risk to select normal embryos to improve the outcomes of assisted reproductive procedures and to avoid the transfer of chromosomally unbalanced and multiple embryos.
Salian S, Vahab SA, Shah H
… +7 more, Shukla A, Ramamurthy B, Shenoy R, Kamath N, Shenoy J, Satyamoorthy K, Girisha KM
Genet Couns
· 2016 · PMID 30226963
We set out to evaluate multiplex ligation dependent probe amplification (MLPA) as a tool for diagnosis and carrier detection in families with a dystrophinopathy. Fifty three Indian families with provisional diagnosis of...We set out to evaluate multiplex ligation dependent probe amplification (MLPA) as a tool for diagnosis and carrier detection in families with a dystrophinopathy. Fifty three Indian families with provisional diagnosis of Duchene muscular dystrophy or Becker muscular dystrophy were evaluated by MLPA and multiplex polymerase chain reaction (PCR). Sanger sequencing was used to analyze the entire gene in one patient. Mothers were tested for carrier status whenever possible. Molecular analysis of DMD gene by combining MLPA and multiplex PCR yielded a mutation detection rate of 62% (33/53). Deletions were detected in 27/53 (51%) cases, duplications in 5/53 (9%) cases, a small deletion one case and Sanger sequencing detected a nonsense mutation in one case. Mutation was not detected in 36% (19/53) cases. Fifty six percent of mothers (9/16) were found to be carriers. MLPA helped to refine the results of multiplex PCR testing in 22 patients (5 duplications, 16 deletions and one small deletion). We also describe a situation where a deletion of single exon on MLPA (but not detected by multiplex PCR) was actually due to a deletion of two nucleotides in the probe ligation site. MLPA appears to score over multiplex PCR in diagnosis and carrier detection, specifically by detecting deletions and duplications that are not detected by traditional multiplex PCR.
Brambila-Tapia AJL, Wegman-Ostrosky T, Garcia-Cruz D
… +5 more, Figuera LE, Castañeda-Cisneros G, Jimenez-Arredondo RE, Sanchez-Corona J, Garcia-Ortiz JE
Genet Couns
· 2016 · PMID 30204973
The appearance of untreated severe hydrocephalus with long-term survival is infrequent; here we report a case with these characteristics, mild neurological alterations and kidney and skeletal anomalies. A female patient...The appearance of untreated severe hydrocephalus with long-term survival is infrequent; here we report a case with these characteristics, mild neurological alterations and kidney and skeletal anomalies. A female patient showed severe hydrocephalus (initially mistaken with hydranencephaly) at 4 years old and left kidney ectopia (initially mistaken with renal agenesis); however, she was derived to the neurology service until she was 12 years old, when she began to present migraine and seizures. At 13 years old the patient was diagnosed with arrested hydrocephalus secondary to aqueduct stenosis, and the seizures worsen thereafter from atonic seizures to complex partial seizures (at 14 years old), presenting generalized seizures at 15 years old. At 17 years old, the seizures were more frequent despite the anticonvulsant treatment and also presented automations, she was also diagnosed with genu recurvatinn and scoliosis. The seizures finally diminished and partially controlled at 19 years old. Despite a cerebral mantle < 2.0 cm at the computer tomography, the patient always presented a satisfactory intellectual development. In this case, the relatively good and long evolution of the severe hydrocephalus is probably related with the late-onset of the disease that permitted a better development of the brain; however, the worsening of the seizures after the hydrocephalus arrested, suggests that arrest is not necessarily associated with a compensation and better evolution of the disease, at least at the beginning of the process. The presence of kidney ectopia and skeletal alterations did not associate with a known genetic disease, however a possible inheritance mechanism is not discarded.
Wolcott-Rallison Syndrome (WRS), also known as Multiple Epiphyseal Dysplasia with Early-onset Diabetes Mellitus is a rare autosomal recessive multisystemic disorder. Its characteristic clinical features are permanent neo...Wolcott-Rallison Syndrome (WRS), also known as Multiple Epiphyseal Dysplasia with Early-onset Diabetes Mellitus is a rare autosomal recessive multisystemic disorder. Its characteristic clinical features are permanent neonatal or early infancy insulin-dependent diabetes and later onset skeletal dysplasia. Other frequent clinical manifestations are hepatic and renal dysfunction, mental retardation, cardiac abnormalities, exocrine pancreatic dysfunction, primary hypothyroidism and neutropenia. This report presents an 8-year-old WRS case who is found to have W522X mutation in EIF2AK3 gene which was only found in two other unrelated Turkish families. W522X mutation in EIF2AK3 gene seems to be confined to Turkey and may be a common mutation in WRS patients from this country. In this paper, we evaluate the clinical features of the patients having W522X mutation and we compare this group with other patients reported to date. Except the characteristic features as diabetes mellitus and epiphyseal dysplasia, all the WRS patients, including patients with W522X mutation, show extensive phenotypic variability that correlates poorly to genotype which suggests that there is no correlation between a specific mutation and the clinical manifestation.
Matthew-Wood syndrome (MWS), also termed Microphthalmia, syndrome 9 (MCOPS9, MIM 601186), Spear syndrome, or pulmonary hypoplasia, diaphragmatic hernia, anophthalmia and cardiac defects syndrome (PDAC syndrome), is an au...Matthew-Wood syndrome (MWS), also termed Microphthalmia, syndrome 9 (MCOPS9, MIM 601186), Spear syndrome, or pulmonary hypoplasia, diaphragmatic hernia, anophthalmia and cardiac defects syndrome (PDAC syndrome), is an autosomal recessive disorder characterised by ocular, respiratory and cardiac abnormalities. Mutations in retinoic acid 6 gene (STRA6) have been reported in clinically diagnosed patients with MWS. Here we presented a case with MWS, who has characteristic findings of the syndrome as well as dextrocardia as an undescribed feature, and bilateral streak gonads which was described only in one patient previously. Molecular analysis showed a homozygous exonic missense mutation in the STRA6 gene.
Öztürk Z, Arhan E, Aydin K
… +6 more, Hirfanoğlu T, Tümer L, Okur I, Serdaroğlu A, Akbaş Y, Karaoğlu B
Genet Couns
· 2016 · PMID 30204970
Cobalamin C (CbIC) deficiency is a rare disorder of vitamin B12 metabolism which results from impaired conversion of both its active forms methylcobalamin and adenosylcobalamin. Early onset cblC typically presents in the...Cobalamin C (CbIC) deficiency is a rare disorder of vitamin B12 metabolism which results from impaired conversion of both its active forms methylcobalamin and adenosylcobalamin. Early onset cblC typically presents in the first year of life with hypotonia, lethargy, seizures, microcephaly, hydrocephalus, developmental delay and other multisystem involvement including hematologic, ocular, renal, hepatic and cardiac symptoms. We report a case of a female infant with cblC deficiency who presented with seizures, developmental delay and hypopigmented cutaneous lesions. To our knowledge, the patient is the first diagnosed with cblC deficiency who had skin hypopigmentation.
Cebi AH, Karaguzel G, Karakus M
… +4 more, Polat R, Seyhan S, Onder H, Ikbal M
Genet Couns
· 2016 · PMID 30204969
Duplications of 20q are rare. Here we report a 15 years old boy with de novo duplication of 17.1 Mb at chromosome 20q. We made a comparison with the other isolated 20q duplication cases. There are phenotypic similarities...Duplications of 20q are rare. Here we report a 15 years old boy with de novo duplication of 17.1 Mb at chromosome 20q. We made a comparison with the other isolated 20q duplication cases. There are phenotypic similarities between the patients who have the same affected chromosomal regions. We also showed a clinical follow up of the patient. There may be a relationship with Glaucoma and Graves disease between the chromosomal region and these diseases may occur at the other patients when they get older.
Dilek FN, Perçin EF, Kayserili H
… +2 more, Ergün MA, Saka N
Genet Couns
· 2016 · PMID 30204968
Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal dysgenesis primarily affect the gonads. Genetic alterations in...Some of the disorders of sex development (DSD), including 46, XX testicular DSD formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal dysgenesis primarily affect the gonads. Genetic alterations in ten unrelated females with complete 46, XY gonadal dysgenesis (GD) were analyzed using an Array 2.7 M platform with whole genome coverage. The analysis result suggested that the most significant region maps to chromosome 8q24.3 which were previously reported by another independent study with a similar patient cohort and this region being probable candidate related to complete 46, XY GD.
Feingold syndrome (FS) is an autosomal dominant hereditary disorder characterised by finger and toe abnormalities, microcephaly, facial dysmorphism, gastrointestinal atresias such primarily as oesophageal and/or duodenal...Feingold syndrome (FS) is an autosomal dominant hereditary disorder characterised by finger and toe abnormalities, microcephaly, facial dysmorphism, gastrointestinal atresias such primarily as oesophageal and/or duodenal atresia and mild to moderate mental retardation. Approximately 60% of cases have an affected parent. MYCN is the only gene in which mutations are known to cause FS. In this report, we present a case with Feingold Syndrome having a novel mutation in MYCN gene and discuss genetic counselling and prenatal diagnosis due to pregnancy of the patient's mother.
Nur BG, Erdogan Y, Curek Y
… +4 more, Akcakus M, Oygur N, Bircan I, Mihci E
Genet Couns
· 2016 · PMID 30204966
Mucolipidosis II or I-cell disease is a rare lysosomal enzyme hydrolase trafficking due to deficient activity of the multimeric enzyme UDP-Nacetylglucosamine-l-phosphotransferase. It is a severe inborn error of lysosomal...Mucolipidosis II or I-cell disease is a rare lysosomal enzyme hydrolase trafficking due to deficient activity of the multimeric enzyme UDP-Nacetylglucosamine-l-phosphotransferase. It is a severe inborn error of lysosomal storage that causes progressive multisystem deterioration and death within the first year of life. The diagnosis of ML II is often difficult in an infant due to clinical variety, phenotypic overlap and the enzyme analysis required. Mucolipidosis II and rickets may have similar physical, biochemical and radiographic findings in newborns. The diagnosis of Mucolipidosis II is often missed, as it may present with rickets-like picture. In this article, we describe two neonatal mucolipidosis II patients mimicking rickets, and we evaluated them by clinical, metabolic and imaging findings via literature and also emphasized the difficulties in diagnosis of this rare disease.
Erol S, Demirel N, Bas AY
… +3 more, Ozcan B, Celik IH, Isik DU
Genet Couns
· 2016 · PMID 30204965
The Joubert syndrome is characterized by hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern and cognitive impairment. The molar tooth sign is the pathognomonic midbrain-hindbrain ma...The Joubert syndrome is characterized by hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern and cognitive impairment. The molar tooth sign is the pathognomonic midbrain-hindbrain malformation for Joubert syndrome. Joubert syndrome and related disorders (JSRD), are the clinically and genetically heterogen disorders in which the obligatory hallmark is the molar tooth sign (MTS). In this report, it was described the association of the molar tooth sign, absence of pituitary gland and corpus callosum agenesis on an infant with JSRD. To the best of our knowledge, this is the first case diagnosed as JSRD and panhypopituitarism without features of OFD VI.
Uctepe E, Aktas D, Alikasifoglu M
… +2 more, Gunduz E, Sonmez FM
Genet Couns
· 2016 · PMID 30204964
The 17q21.31 microdeletion syndrome is characterized by intellectual disability, epilepsy, facial dysmorphism and friendly behavior. Recently, KANSLJ gene has been considered as a major causal gene for this phenotype. He...The 17q21.31 microdeletion syndrome is characterized by intellectual disability, epilepsy, facial dysmorphism and friendly behavior. Recently, KANSLJ gene has been considered as a major causal gene for this phenotype. Here we report on two Turkish patients with different seizure types and additional dysmorphic features associated with 17q21.31 microdeletion syndrome. A 4 year-old female patient with generalized tonic-clonic seizures, mild mental retardation, dysmorphic features and friendly behavior and a 14 years-old female with intractable epilepsy, different dysmorphic features, severe mental and motor retardation and self-mutilation were evaluated by array-based comparative genomic hybridization (microarray CGH). Array CGH identified 17q21.31 microdeletion that contains MAP7 CRHR1, KANSLI, PLEKHMI genes in case I and CRHR1, PLEKHM but not KANSLJgenes in case 2. To the best of our knowledge this is the first report of a patient with the 17q21.31 microdeletion which does not encompass KANSLI gene. These data imply another gene or genes causing similar phenotype in this patient.
Bilgili SG, Karadag AS, Calka O
… +2 more, Onder S, Bayram I
Genet Couns
· 2016 · PMID 30204963
Ichthyosis Linearis Circumfiexa (ILC) is a rarely seen autosomal recessive keratinization disorder and is characterized by erythematous, polycystic, plaques with 'double-edged' scales. Its histological features resemble...Ichthyosis Linearis Circumfiexa (ILC) is a rarely seen autosomal recessive keratinization disorder and is characterized by erythematous, polycystic, plaques with 'double-edged' scales. Its histological features resemble psoriasis. A triad of ichthyosis (usually Ichthyosis Linearis Circumfiexa), trichorrhexis invaginata (a distinctive hair shaft disorder) and atopy is named as Netherton syndrome. Herein, we report a 12 year-old girl presenting with ILC not accompanied with typical atopy findings and hair shaft disorder.
Infants with limb reduction deficiencies (LRD) often have other associated congenital anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in a defined populatio...Infants with limb reduction deficiencies (LRD) often have other associated congenital anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in a defined population. The associated anomalies in infants with LRD were collected in all livebirths, stillbirths and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 317 infants bom with LRD during this period, representing a prevalence of 8.2 per 10,000, 59.9% had associated anomalies. There were 27 (8.5%) cases with chromosomal abnormalities including 17 trisomies 18, and 73 (23.0%) nonchromosomal recognized dysmorphic conditions including 19 VA(C)TER(L) association and 15 Poland syndrome. However, numerous other recognized dysmorphic conditions were registered. Ninety (28.4%) of the cases had multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the cardiac, the urogenital, and the central nervous system were the most common other anomalies. This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. Therefore the overall prevalence of associated anomalies, which was more than one in two infants, emphasizes the need for a thorough investigation of infants with LRD. A routine screening for other anomalies especially in the musculoskeletal system, the cardiovascular system, the urogenital system, the central nervous system, and the digestive system may be considered in infants and in fetuses with LRD.
Pelc M, Ciara E, Jezela-Stanek A
… +1 more, Krajewska-Walasek M
Genet Couns
· 2016 · PMID 30204961
Mutations leading to dysregulation of the Ras/MAPK signal transduction cascade are a common cause of Noonan syndrome (NS) and play a key role in the pathogenesis of many human malignancies. To date, about 24 various RAF1...Mutations leading to dysregulation of the Ras/MAPK signal transduction cascade are a common cause of Noonan syndrome (NS) and play a key role in the pathogenesis of many human malignancies. To date, about 24 various RAF1 germline mutations were identified in NS. The incidence of malignancies in NS patients with RAF1 mutations has not been reported so far. However, in a few cases somatic RAF1 mutations were observed in cancer, including two described in therapy-related acute myeloid leukaemia (t-AML). We present a case of an adult female patient with Noonan syndrome and her affected mother with a rare RAF] germline mutation c.1279A>G (p.S427G), located within the highly conserved domain (CR3) of serine/threonine kinase C-RAF. Interestingly, this mutation has been reported for the first time in a patient with t-AML as a somatic change and so far has been identified in only one individual with NS phenotype and his mother. Our report presents the second familial case of Noonan syndrome due to a germline p.S427G substitution in RAF] with no occurrence of a malignant tumor. It may suggest that carrying a germline mutation in the RAF1 oncogene is not associated with an increased risk of tumor development. Since RAF1 mutations have been observed as a somatic event in many types of cancer, this report might be of importance for the genetic counselling and management of patients both with germline and somatic alterations in this gene.
Ismail S, Essawi M, Sedky N
… +17 more, Hassan H, Fayez A, Helmy N, Shehab M, Farouk D, Elruby M, Otaify G, Eldarsh A, Hosny L, Gaber K, Aboul-Ezz EHA, Ramzy MI, Mehrez MI, Hassib NF, Elhadidi SMA, Aglan MS, Temtamy SA
Genet Couns
· 2016 · PMID 30204960
The Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by mutation in ESCO2 gene. Among over 150 reported international cases, 16 cases are Egyptian including the presently reported patients. The curren...The Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by mutation in ESCO2 gene. Among over 150 reported international cases, 16 cases are Egyptian including the presently reported patients. The current study reports 8 new Egyptian patients from 7 unrelated consanguineous families investigating clinical phenotype as well as cytogenetic changes in all cases and mutational spectrum in 4 cases. Clinical, orodental, cytogenetic and molecular studies were done to investigate genotype/phenotype correlation. Evaluation of the studied 8 patients showed that they all exhibited the main limb and craniofacial features of Roberts syndrome. Cytogenetic studies including centromeric separation and puffing by Giemsa and DAPI stains and for the first time in Egypt analysis for premature centromeric division by FISH showed consistent centromeric separation in all studied cases. Molecular studies of 4 available patients showed that they all have ESCO2 gene mutation. We conclude that RBS has a well-defined clinical spectrum. The cytogenetic changes are due to sister chromatid cohesion defects which lead to mitotic dysfunction. We confirmed previous results of lack of genotype/phenotype correlation. We also confirmed that the severity of limb malformation correlates with craniofacial manifestations. We recommend detailed evaluation of orodental changes for further definition of the phenotype and for proper patient management. We emphasize the need for further studies for the frequency of premature centromeric separation by FISH as a possible indicator of phenotypic severity.