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1.
Indian Pediatr ; 2019 Jul; 56(7): 556-559
Artigo | IMSEAR | ID: sea-199407

RESUMO

Objective: To study the histopathological characteristics and mutation spectrum of patientspresenting with the Duchenne muscular dystrophy (DMD) phenotype. Methods: This wasa descriptive study conducted over a period of 8 years. Multiplex ligation-dependent probeamplification (MLPA) was done in patients presenting with the DMD phenotype. If MLPA wasnegative, patients were offered muscle biopsy for histopathological studies and/or nextgeneration sequencing (NGS) based multigene panel testing for muscular dystrophies.Results: Of the 510 patients included, mutation in the DMD gene was detected by MLPA in372 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonicduplications. Exons 45-55 were most commonly involved in large deletions and exons 1-10were the commonest exons involved in duplications. In the MLPA-negative cohort, 27proceeded for muscle biopsy. NGS was done in 14 patients, 10 of whom had pathogenicmutations in the DMD gene, 3 were non dystrophinopathies and no pathogenic variant couldbe identified in one patient. Conclusions: For patients presenting with the DMD phenotype,MLPA of the DMD gene has a high diagnostic rate of about 73%, and non-dystrophinopathies may constitute a small but significant proportion.

2.
Artigo em Inglês | IMSEAR | ID: sea-170335

RESUMO

Background & objectives: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations. Methods: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein. Results: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population. Interpretation & conclusions: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI.

3.
Artigo em Inglês | IMSEAR | ID: sea-155334

RESUMO

Background & objectives: Camptodactyly – arthropathy- coxa vara- pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations in the PRG4 (proteoglycan 4) gene. Hallmarks of the syndrome include congenital or early-onset camptodactyly and arthropathy with synovial hyperplasia, progressive coxa vara deformity and non-inflammatory pericardial effusions. Till date only around 25 pathogenic mutations have been reported in this gene and none have been reported from India. We report here the mutations in the PRG4 gene in three patients of CACP from two unrelated families from India. Methods: Molecular genetic studies were done for the three patients with the CACP syndrome, from two unrelated Indian families, through sequence analysis of all coding exons and the exon-intron boundaries of the PRG4 gene. Results: Two novel frame-shift deletion mutations leading to premature protein termination were found. One patient was identified to be homozygous for a 2 base pair deletion in exon 6 (c.2645_2646delGA) and the two affected siblings from the other family were found to be homozygous for a 4 base pair deletion in exon 6 (c.2883_2886delAAGA). Conclusions: This is perhaps the first report of PRG4 mutations from India. Further mutation studies in Indian CACP cases will help to determine the mutation spectrum of the PRG4 gene in the Indian population and also help to further elucidate the molecular pathology and the genotype-phenotype correlation of this rare disease.

5.
Indian Pediatr ; 2012 October; 49(10): 799-804
Artigo em Inglês | IMSEAR | ID: sea-169491

RESUMO

Background: There is limited literature available on the phenotypic and mutation spectrum of Indian patients with Lysosomal storage disorders (LSD). Objective: To elucidate the clinical, biochemical and mutation spectrum and to study the management options in Indian patients with lysosomal storage disorders. Design: Descriptive study. Subjects and Methods: All patients with lysosomal storage disorders diagnosed in the Medical Genetics department of a tertiary care institute in North India over a three year period from January 2008 to December 2010. Results: Out of the total of 93 patients clinically suspected to have LSDs, 68 (mean age at presentation 4.5 years) were confirmed to have LSDs based on the laboratory/neuroimaging findings and documentation of deficient enzymatic activity in the peripheral blood (leucocytes or plasma) and/or skin fibroblasts. The commonest clinical features at presentation were growth retardation (failure to thrive 47.2% and short stature 17.6%), hepatosplenomegaly (41.2%) and neuroregression (33.8%). A history of consanguinity was present in 32.4% of the families. Prenatal diagnosis was done in a total of 6 affected families; two pregnancies were found to be affected (one each with Gaucher disease and Tay Sachs disease) and in both cases the parents opted for termination of pregnancy. Of the remaining four pregnancies which were found to be unaffected and therefore continued, three were confirmed to be normal on post-natal follow up. Enzyme replacement therapy (ERT) is being given for a total of 8 LSD patients and all of them are showing a gradual amelioration of their symptoms and an improvement in the quality of life. Conclusions: Lysosomal storage disorders constitute an important group of genetic metabolic disorders for many of which therapeutic options are now available.

6.
Indian J Pediatr ; 2006 Jul; 73(7): 609-15
Artigo em Inglês | IMSEAR | ID: sea-83845

RESUMO

OBJECTIVE: Hemihyperplasia is a heterogenous group of disorders characterized by asymmetric limb growth. There is considerable confusion regarding their classification and ascertainment into various syndromes. We tried to look into the various aspects of hemihyperplasia syndromes. METHODS: Records of 17 consecutive cases of hemihyperplasia were reviewed and were ascertained into various syndromes based on available literature and diagnostic criteria. RESULTS: Of the 17 cases with hemihyperplasia, 3 cases satisfied the diagnostic criteria for Proteus syndrome. One patient each was ascertained as Klippel Trenaunay Weber syndrome and Hemihyperplasia- Multiple lipomatosis. 9 cases were classified as isolated hemihyperplasia. We found two novel associations with hemihyperplasia; namely Ehlers-Danlos syndrome like skin changes and Poland anomaly on the affected side. The remaining 3 cases had miscellaneous disorders with limb asymmetry, namely Neurofibromatosis Type I in 2 cases and Olliers disease in one case. CONCLUSION: Efforts to diagnose syndromes of hemihyperplasia help in genetic counseling.


Assuntos
Adolescente , Criança , Pré-Escolar , Extremidades/crescimento & desenvolvimento , Feminino , Transtornos do Crescimento/diagnóstico , Humanos , Lactente , Masculino , Síndrome
7.
Indian Heart J ; 2006 Jul-Aug; 58(4): 330-5
Artigo em Inglês | IMSEAR | ID: sea-4349

RESUMO

OBJECTIVE: Angiotensin-converting enzyme plays an important role in maintaining blood pressure, while methylenetetrahydrofolate reductase is involved in homocysteine metabolism. As hypertension and elevated homocysteine levels are among the various risk factors for coronary artery disease, the two polypeptides might need to be considered while determining the risk. Our study aimed to assess the association between common polymorphisms in these genes and susceptibility to coronary artery disease. METHODS: We studied 268 north Indian individuals with coronary artery disease and 90 age-matched controls. The distribution of the genotypes and allele frequencies of both genes were analyzed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis. RESULTS: The frequency of the D allele was significantly higher among the patients (62%) than the controls (44%) (p=0.001, odds ratio=2.06). The same goes for the DD genotype (37% vs 21%) (p=0.004). The combined frequency of the D allele carriers was significantly higher among patients of coronary heart disease, with a difference of 20% (85% vs 65%) (p=0.003, odds ratio=3.1; CI: 1.3-7.29). However, the frequency of the T and C alleles, as well as that of the CC, CT and TT genotypes of the methylenetetrahydrofolate reductase gene, did not differ significantly between the two groups. CONCLUSION: We conclude that coronary artery disease in north Indian patients is strongly associated with the carrier state of the angiotensin-converting enzyme D allele, but not with the C677T transition in the methylenetetrahydrofolate reductase gene.


Assuntos
Adulto , Idoso , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Genótipo , Humanos , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Adulto Jovem
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