Indian J Hum Genet
· 2013 Jan · PMID 23901187
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BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder in children. The disorder is caused mainly due to mutations in Nipped-B-like protein. The molecular data for CdLS is available from de...BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder in children. The disorder is caused mainly due to mutations in Nipped-B-like protein. The molecular data for CdLS is available from developed countries, but not available in developing countries like India. In the present study, the hotspot region of NIPBL gene was screened by Polymerase Chain Reaction which includes exon 2, 22, 42, and a biggest exon 10, in six CdLS patients and ten controls. MATERIALS AND METHODS: The method adopted in present study was amplification of the target exon by using polymerase chain reaction, qualitative confirmation of amplicons by Agarose Gel Electrophoresis and use of amplicons for Conformation Sensitive Gel Electrophoresis to find heteroduplex formation followed by sequencing. RESULTS: We report two polymorphisms in the studied region of gene NIPBL. The polymorphisms are in the region of intron 1 and in exon 10. The polymorphism C/A is present in intron 1 region and polymorphism T/G in exon 10. CONCLUSION: The intronic region polymorphism may have a role in intron splicing whereas the polymorphism in exon 10 results in amino acid change (Val to Gly). These polymorphisms are disease associated as these are found in CdLS patients only and not in controls.
Indian J Hum Genet
· 2013 Jan · PMID 23901186
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The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology....The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.
Indian J Hum Genet
· 2012 Sep · PMID 23716954
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Orofaciodigital syndrome type-VI (Varadi-Papp Syndrome) is a rare autosomal recessive disorder characterized by variable orofacial anomalies, central polydactyly of the hands, and cerebellar dysgenesis (mainly hypoplasia...Orofaciodigital syndrome type-VI (Varadi-Papp Syndrome) is a rare autosomal recessive disorder characterized by variable orofacial anomalies, central polydactyly of the hands, and cerebellar dysgenesis (mainly hypoplasia or aplasia of vermis, rarely Dandy-Waker anomaly). Here a case of Varadi-Papp syndrome with recurrent episodic tachypnea-apnea, minimal orofacial features, several Y-shaped metacarpals, and cerebellar vermis hypoplasia, diagnosed in the neonatal age, is reported for the first time in Indian literature. The importance of early accurate diagnosis of this rare disease for proper genetic counseling and prenatal case detection of pregnancy at risk is also emphasized as the prognosis is poor in almost all cases.
We present a case of seven nipples in a 32-year-old male patient. The patient had two regular nipples along with five supernumerary nipples. Usually, supernumerary nipples develop along the two vertical "milk lines" whic...We present a case of seven nipples in a 32-year-old male patient. The patient had two regular nipples along with five supernumerary nipples. Usually, supernumerary nipples develop along the two vertical "milk lines" which start in the arm pit on each side, run down through the typical nipples, and end at the groin. Our patient had six nipples which confirm to the "milk lines" and one nipple which was above the umbilicus in the midline and did not confirm to the "milk lines." To our knowledge, this is the second case report with seven nipples in the world.
Sandhya DG, Ahmed F, Khadke K
… +2 more, Murthy SS, Rajappa SJ
Indian J Hum Genet
· 2012 Sep · PMID 23716952
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Acute myeloid leukemia with maturation (AML-M2) is associated with the 8;21 translocation. For the first time in an adult patient with AML-M2, a novel unbalanced translocation involving the short arm of chromosome 11 and...Acute myeloid leukemia with maturation (AML-M2) is associated with the 8;21 translocation. For the first time in an adult patient with AML-M2, a novel unbalanced translocation involving the short arm of chromosome 11 and long arm of chromosome18 with new breakpoints is presented. CD82 on band 11p11.2 and GATA 6 on 18q11.2 may play a role in the pathogenesis of de novo AML M2. The report with translocation (11;18)(p11.2;q11.2), as the sole cytogenetic abnormality provides more data on the leukemogenesis of de novo AML M2.
Indian J Hum Genet
· 2012 Sep · PMID 23716951
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A 14-month-old boy with overlapping features of Townes-Brocks syndrome (TBS) and single median maxillary incisor syndrome (SMMCIS) is being reported with brief review of the above syndromes and possible differential diag...A 14-month-old boy with overlapping features of Townes-Brocks syndrome (TBS) and single median maxillary incisor syndrome (SMMCIS) is being reported with brief review of the above syndromes and possible differential diagnosis.
Hama I, Ilham R, Ouzeddoun N
… +3 more, Alhamany Z, Bayahia R, Sefiani A
Indian J Hum Genet
· 2012 Sep · PMID 23716950
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Familial Mediterranean fever (FMF, MIM 249100) is an autosomal recessive disease affecting mainly patients of the Mediterranean basin. It is an autoinflammatory periodic disorder characterized by recurrent episodes of fe...Familial Mediterranean fever (FMF, MIM 249100) is an autosomal recessive disease affecting mainly patients of the Mediterranean basin. It is an autoinflammatory periodic disorder characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The major complication of FMF is the development of renal AA amyloidosis. Treatment with colchicine prevents the occurrence of recurrent seizures and renal amyloidosis. The disease is caused by mutations in the MEFV gene. We report here the cases of two unrelated patients, who have been late diagnosed with FMF complicated by renal amyloidosis. We focus on the importance of early diagnosis of FMF, both to start rapidly treatment with colchicine and avoid renal amyloidosis, and to provide genetic counseling to families.
Singh R, Kaleem AM, Narayana SS
… +1 more, Mahdi AA
Indian J Hum Genet
· 2012 Sep · PMID 23716949
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Y-chromosomal microdeletions are associated with severe oligozoospermia or azoospermia. AZFc microdeletions have been always associated with severe oligozoospermia or azoospermia with a rare occurrence in individuals wit...Y-chromosomal microdeletions are associated with severe oligozoospermia or azoospermia. AZFc microdeletions have been always associated with severe oligozoospermia or azoospermia with a rare occurrence in individuals with other infertility phenotypes. We report here a rare case of an infertile man carrying AZFc deletion, whose semen picture is oligoasthenoteratozoospermia complexed with seminal oxidative stress. Anti-oxidant therapy could make no change in either oxidative stress biomarker levels of semen, seminal parameters or serum hormone levels. Therefore, oligoasthenoteratozoospermia in the present case correlates with AZFc deletion, and high content of abnormal sperm eventually might be responsible for persistently elevated reactive oxygen species levels. Understanding the function of genes in AZFc region could help decipher the exact cause of the phenotype in such cases.
Talari K, Subbanna PK, Amalnath D
… +1 more, Suri SD
Indian J Hum Genet
· 2012 Sep · PMID 23716948
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Proteus syndrome (PS) is a rare hamartomatous disorder characterized by various cutaneous and subcutaneous lesions, including vascular malformations, lipomas, hyperpigmentation, and several types of nevi. Partial giganti...Proteus syndrome (PS) is a rare hamartomatous disorder characterized by various cutaneous and subcutaneous lesions, including vascular malformations, lipomas, hyperpigmentation, and several types of nevi. Partial gigantism with limb or digital overgrowth is pathognomonic of PS. We report a rare case of PS in a 50-year-old man who presented with inferior wall myocardial infarction and was incidentally detected to have hypertrophy of index and middle fingers of both the hands.
Mutesa L, Jamar M, Hellin AC
… +2 more, Pierquin G, Bours V
Indian J Hum Genet
· 2012 Sep · PMID 23716947
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While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present observation, a boy wi...While the XYY and XXYY syndromes have been several time described in patients, the combination of both syndromes in an individual is a rare event and may result in a severe phenotype. In the present observation, a boy with congenital scoliosis due to segmented thoracic hemivertebra associated with radioulnar synostosis and congenital heart disease is described. Chromosome G-banding and FISH analysis demonstrated a de novo mosaic karyotype 48, XXYY/47, XYY in this patient. To the best of our knowledge, this is the first report of a combination of XYY and XXYY syndromes.
Venkataswamy E, Nargund AR, Prabhudesai S
… +8 more, Patil GV, Chandra RJ, Veldore VH, Patil S, Verma A, Sahoo R, Ajaikumar BS, Prasannakumari
Indian J Hum Genet
· 2012 Sep · PMID 23716946
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Del(5)(q) is a common chromosomal abnormality with favourable prognosis in Myelodysplastic Syndrome (MDS) and Acute myeloid leukemia (AML). However, del(5)(q) is also seen rarely in Acute lymphoblastic leukemia (ALL) and...Del(5)(q) is a common chromosomal abnormality with favourable prognosis in Myelodysplastic Syndrome (MDS) and Acute myeloid leukemia (AML). However, del(5)(q) is also seen rarely in Acute lymphoblastic leukemia (ALL) and its significance remains poorly understood. We present here, a case report of diagnosis of an adult 75 year old patient of ALL with a cytogenetic abnormality of del(5)(q32). His clinical features, morphology and immunophenotyping findings were suggestive of T-ALL. Relevant literature has been reviewed and discussed.
Girisha KM, Shrikiran A, Bidchol AM
… +3 more, Sakamoto O, Gopinath PM, Satyamoorthy K
Indian J Hum Genet
· 2012 Sep · PMID 23716945
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We report on a girl with methylmalonic acidemia, cblA type with a novel homozygous mutation and describe the clinical phenotype and response to therapy.We report on a girl with methylmalonic acidemia, cblA type with a novel homozygous mutation and describe the clinical phenotype and response to therapy.
Chhavi N, Prashanth S, Venkatesh C
… +1 more, Karthikeyan K
Indian J Hum Genet
· 2012 Sep · PMID 23716944
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A male neonate was born with rhizomelic shortening of limbs. Skeletal radiograph showed punctate calcification of epiphysis of humerus, femur, and tibia. The diagnosis and a brief review of literature pertaining to the c...A male neonate was born with rhizomelic shortening of limbs. Skeletal radiograph showed punctate calcification of epiphysis of humerus, femur, and tibia. The diagnosis and a brief review of literature pertaining to the condition with emphasis on antenatal diagnosis and counseling are being reported.
Shirazi HA, Hedayati M, Daneshpour MS
… +2 more, Shafiee A, Azizi F
Indian J Hum Genet
· 2012 Sep · PMID 23716943
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MATERIAL AND METHODS: 22 nuclear families (78 persons including 12 patients) with papillary and follicular tumors were selected in a period of six months from Milad hospital. Five microsatellite markers (D19S413, D19S391...MATERIAL AND METHODS: 22 nuclear families (78 persons including 12 patients) with papillary and follicular tumors were selected in a period of six months from Milad hospital. Five microsatellite markers (D19S413, D19S391, D19S916, D19S568, D19S865) on 19p13.2 were selected for genetic analysis. Genomic DNAs was extracted; PCR and polyacrylamide gel electrophoresis method were used for variation detection. RESULTS: The results show that 5.4% of the follicular carcinomas and 17.9% of the papillary carcinomas presented LOH at recognition sites. LOH of Papillary carcinoma detected about 13.9% and follicular carcinoma 7.2% in this study. The frequency of informative cases was not similar for each marker: D19S413 (41.1%)[1], D19S391 (12.5%), D19S916 (10.7%), D19S568 (1.8%) and D19S865 (3.6%). Loss of hetrozygosity in D19S413 predicts the relation between variation in this region and the disease. DISCUSSION: Our findings showed an average of 13.9% LOH in FNMTC cases. Among the five major microsatellites, D19S413 was the most informative for LOH analysis of FNMTC.
Indian J Hum Genet
· 2012 Sep · PMID 23716942
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BACKGROUND: Oral clefts having a prehistoric existence and the latest scientific technologies have shown new insights in identifying the cause and management. So this is a DNA/gene based study has been presented in this...BACKGROUND: Oral clefts having a prehistoric existence and the latest scientific technologies have shown new insights in identifying the cause and management. So this is a DNA/gene based study has been presented in this article which comprises the significance of MSX1 gene in cleft samples of major states of South India. AIMS: To evaluate the significance of MSX1 gene in South Indian population having cleft lip and palate. SETTINGS AND DESIGN: Four states of native population were set for the study. From each state renowned cleft operating center was selected with the prior ethical and suitable permission and patient consent was taken. Blood samples were collected from each effected sibling were studied and their details were coded. The collected blood samples were used for DNA isolation, PCR amplification and sequencing. MATERIALS AND METHODS: Eighty patients with non-syndromic CL/CLP/CP from various cleft operating centers in southern states (Karnataka, Tamilnadu, Kerala and Andhra Pradesh) with different ethnic/cultural background were taken. Twenty samples (families) were collected from each state and sequenced and compared with earlier data. RESULTS: Analysis of this study indicates that mutation of either G273A/C or C102G seems to cause cleft formation. In this analysis, we found a novel mutation (414G to T) which is submitted to NCBI Gene data bank (EF065625). CONCLUSION: This study supports MSX1 gene leading to cleft lip and palate in the samples studied.
Indian J Hum Genet
· 2012 Sep · PMID 23716941
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CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of c...CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 (*)2, (*)3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 ((*)2, F(*)3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 (*)2, CYP2C9 (*)3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes.
Indian J Hum Genet
· 2012 Sep · PMID 23716940
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AIMS: This study was designed to determine the prevalence of azoospermia factor (AZF) microdeletions on the Y chromosome in Sri Lankan Sinhalese infertile men with azoospermia and severe oligozoospermia. SETTINGS AND DES...AIMS: This study was designed to determine the prevalence of azoospermia factor (AZF) microdeletions on the Y chromosome in Sri Lankan Sinhalese infertile men with azoospermia and severe oligozoospermia. SETTINGS AND DESIGN: The patient group was 207 karyotypically normal infertile Sinhalese males. MATERIALS AND METHODS: The presence of 13 sequence-tagged site (STS) markers in the AZF region was tested using multiplex polymerase chain reaction (M-PCR). One hundred and twenty unselected men were also studied as a control group. RESULTS: Three (1.5%) had classic Y chromosome microdeletions in the AZFc sub-region. CONCLUSIONS: These results suggest a much lower Y chromosome microdeletion frequency than previously thought, even among a strictly selected group of sub-fertile males in Sri Lanka.