Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families

Shazia Micheal; Ilse Therésia Gabriëla Niewold; Sorath Noorani Siddiqui; Saemah Nuzhat Zafar; Muhammad Imran Khan; Arthur A B Bergen

doi:10.3390/genes9020112

Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families

Shazia Micheal, Ilse Therésia Gabriëla Niewold, Sorath Noorani Siddiqui, Saemah Nuzhat Zafar, Muhammad Imran Khan, Arthur A B Bergen

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Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the geneGJA3. Sanger sequence analysis of theGJA3gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance forGJA3gene mutations in cataract was autosomal dominant (AD) only. The screening of additional probands (n= 41) of cataract families revealed a previously known mutation c.56C>T p.(Thr19Met) inGJA3gene. In addition, sequencing of the exon-intron boundaries of theGJA8gene in 41 cataract probands revealed two additional mutations: a novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co-segregating with the disease phenotype in an AD manner. All these mutations are predicted to be pathogenic by in silico analysis and were absent in the control databases. In conclusion, results of the current study enhance our understanding of the genetic basis of cataract, and identified the involvement of theGJA3in the disease etiology in both AR and AD manners.

Originele taal-2	Engels
Artikelnummer	E112
Tijdschrift	Genes
Volume	9
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.3390/genes9020112
Status	Gepubliceerd - 2018

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title = "Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families",

abstract = "Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the geneGJA3. Sanger sequence analysis of theGJA3gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance forGJA3gene mutations in cataract was autosomal dominant (AD) only. The screening of additional probands (n= 41) of cataract families revealed a previously known mutation c.56C>T p.(Thr19Met) inGJA3gene. In addition, sequencing of the exon-intron boundaries of theGJA8gene in 41 cataract probands revealed two additional mutations: a novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co-segregating with the disease phenotype in an AD manner. All these mutations are predicted to be pathogenic by in silico analysis and were absent in the control databases. In conclusion, results of the current study enhance our understanding of the genetic basis of cataract, and identified the involvement of theGJA3in the disease etiology in both AR and AD manners.",

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author = "Shazia Micheal and Niewold, {Ilse Ther{\'e}sia Gabri{\"e}la} and Siddiqui, {Sorath Noorani} and Zafar, {Saemah Nuzhat} and Khan, {Muhammad Imran} and Bergen, {Arthur A B}",

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Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families. / Micheal, Shazia; Niewold, Ilse Therésia Gabriëla; Siddiqui, Sorath Noorani et al.
In: Genes, Vol. 9, Nr. 2, E112, 2018.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

TY - JOUR

T1 - Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families

AU - Micheal, Shazia

AU - Niewold, Ilse Therésia Gabriëla

AU - Siddiqui, Sorath Noorani

AU - Zafar, Saemah Nuzhat

AU - Khan, Muhammad Imran

AU - Bergen, Arthur A B

PY - 2018

Y1 - 2018

N2 - Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the geneGJA3. Sanger sequence analysis of theGJA3gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance forGJA3gene mutations in cataract was autosomal dominant (AD) only. The screening of additional probands (n= 41) of cataract families revealed a previously known mutation c.56C>T p.(Thr19Met) inGJA3gene. In addition, sequencing of the exon-intron boundaries of theGJA8gene in 41 cataract probands revealed two additional mutations: a novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co-segregating with the disease phenotype in an AD manner. All these mutations are predicted to be pathogenic by in silico analysis and were absent in the control databases. In conclusion, results of the current study enhance our understanding of the genetic basis of cataract, and identified the involvement of theGJA3in the disease etiology in both AR and AD manners.

AB - Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the geneGJA3. Sanger sequence analysis of theGJA3gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance forGJA3gene mutations in cataract was autosomal dominant (AD) only. The screening of additional probands (n= 41) of cataract families revealed a previously known mutation c.56C>T p.(Thr19Met) inGJA3gene. In addition, sequencing of the exon-intron boundaries of theGJA8gene in 41 cataract probands revealed two additional mutations: a novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co-segregating with the disease phenotype in an AD manner. All these mutations are predicted to be pathogenic by in silico analysis and were absent in the control databases. In conclusion, results of the current study enhance our understanding of the genetic basis of cataract, and identified the involvement of theGJA3in the disease etiology in both AR and AD manners.

KW - Journal Article

U2 - 10.3390/genes9020112

DO - 10.3390/genes9020112

M3 - Article

C2 - 29461512

SN - 2073-4425

VL - 9

JO - Genes

JF - Genes

IS - 2

M1 - E112

ER -

Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families

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