Dataset Information

Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients.

ABSTRACT: AIM:To find the CYP1B1 mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees. METHODS:After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of CYP1B1 gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function. RESULTS:Sequencing analysis revealed 5 different CYP1B1 variants in 7 families (7/11; 64%), including two novel variants. A common mutation, p.R390H was found in four families, whereas p.P437L was found once in a family. Two novel variants, a homozygous non sense variant p.L13* and a compound heterozygous variant, p.P350T along with p.V364M were segregating with PCG in two families. All the patients had the variable onset and severity of the disease. The success rate of early clinical interventions was observed dependent on mutation types and position. Two different haplotypes were associated with frequently found mutation, p.R390H. CONCLUSION:Identification of novel CYP1B1 variants reassert the genetic heterogeneity of Pakistani PCG patients. The patients with missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of CYP1B1 mutations in the development of PCG and its course of pathogenicity.

SUBMITTER: Waryah YM

PROVIDER: S-EPMC6326927 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Two novel variants in <i>CYP1B1</i> gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients.

Waryah Yar Muhammad YM Iqbal Muhammad M Sheikh Shakeel Ahmed SA Baig Muhammad Azhar MA Narsani Ashok Kumar AK Atif Muhammad M Bhinder Munir Ahmad MA Ur Rahman Attiq A Memon Azam Iqbal AI Pirzado Muhammad Suleman MS Waryah Ali Muhammad AM

International journal of ophthalmology 20190118 1

<h4>Aim</h4>To find the <i>CYP1B1</i> mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees.<h4>Methods</h4>After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundari ...[more]

PMID: 30662834

Similar Datasets

Project description:Background and objectivesThe term autosomal recessive cerebellar ataxia (ARCA) encompasses a diverse group of heterogeneous degenerative disorders of the cerebellum. Spinocerebellar ataxia autosomal recessive 10 (SCAR10) is a distinct classification of cerebellar ataxia caused by variants in the ANO10 gene. Little is known about the molecular role of ANO10 or its role in disease. There is a wide phenotypic spectrum among patients, even among those with the same or similar genetic variants. This study aimed to characterize the molecular consequences of variants in ANO10 and determine their pathologic significance in patients diagnosed with SCAR10.MethodsWe presented 4 patients from 4 families diagnosed with spinocerebellar ataxia with potential pathogenic variants in the ANO10 gene. Patients underwent either clinical whole-exome sequencing or screening of a panel of known neuromuscular disease genes. Effects on splicing were studied using reverse transcriptase PCR to analyze complementary DNA. Western blots were used to examine protein expression.ResultsOne individual who presented clinically at a much earlier age than typical was homozygous for an ANO10 variant (c.1864A > G [p.Met622Val]) that produces 2 transcription products by altering an exonic enhancer site. Two patients, both of Lebanese descent, had a homozygous intronic splicing variant in ANO10 (c.1163-9A > G) that introduced a cryptic splice site acceptor, producing 2 alternative transcription products and no detectable wild-type protein. Both these variants have not yet been associated with SCAR10. The remaining patient was found to have compound heterozygous variants in ANO10 previously associated with SCAR10 (c.132dupA [p.Asp45Argfs*9] and c.1537T > C [p.Cys513Arg]).DiscussionWe presented rare pathogenic variants adding to the growing list of ANO10 variants associated with SCAR10. In addition, we described an individual with a much earlier age at onset than usually associated with ANO10 variants. This expands the phenotypic and allelic heterogeneity of ANO10-associated ARCA.

Dataset Information

Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients.

Publications

Two novel variants in <i>CYP1B1</i> gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets