Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families
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...
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2018-02-01
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| Series: | Genes |
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| Online Access: | http://www.mdpi.com/2073-4425/9/2/112 |
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doaj-4b45cc6f72894d84b500e7372f9be0712020-11-24T22:27:34ZengMDPI AGGenes2073-44252018-02-019211210.3390/genes9020112genes9020112Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract FamiliesShazia Micheal0Ilse Therésia Gabriëla Niewold1Sorath Noorani Siddiqui2Saemah Nuzhat Zafar3Muhammad Imran Khan4Arthur A. B. Bergen5Department of Clinical Genetics, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Clinical Genetics, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsDepartment of Pediatric Ophthalmology and Strabismus, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi 46000, PakistanDepartment of Pediatric Ophthalmology and Strabismus, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi 46000, PakistanDepartment of Human Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, The NetherlandsDepartment of Clinical Genetics, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The NetherlandsCongenital 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 gene GJA3. Sanger sequence analysis of the GJA3 gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance for GJA3 gene 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) in GJA3 gene. In addition, sequencing of the exon-intron boundaries of the GJA8 gene 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 the GJA3 in the disease etiology in both AR and AD manners.http://www.mdpi.com/2073-4425/9/2/112congenital cataracthomozygosity mappingsanger sequencingprobandGJA3 geneGJA8mutationsegregation |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Shazia Micheal Ilse Therésia Gabriëla Niewold Sorath Noorani Siddiqui Saemah Nuzhat Zafar Muhammad Imran Khan Arthur A. B. Bergen |
| spellingShingle |
Shazia Micheal Ilse Therésia Gabriëla Niewold Sorath Noorani Siddiqui Saemah Nuzhat Zafar Muhammad Imran Khan Arthur A. B. Bergen Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families Genes congenital cataract homozygosity mapping sanger sequencing proband GJA3 gene GJA8 mutation segregation |
| author_facet |
Shazia Micheal Ilse Therésia Gabriëla Niewold Sorath Noorani Siddiqui Saemah Nuzhat Zafar Muhammad Imran Khan Arthur A. B. Bergen |
| author_sort |
Shazia Micheal |
| title |
Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families |
| title_short |
Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families |
| title_full |
Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families |
| title_fullStr |
Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families |
| title_full_unstemmed |
Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families |
| title_sort |
delineation of novel autosomal recessive mutation in gja3 and autosomal dominant mutations in gja8 in pakistani congenital cataract families |
| publisher |
MDPI AG |
| series |
Genes |
| issn |
2073-4425 |
| publishDate |
2018-02-01 |
| description |
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 gene GJA3. Sanger sequence analysis of the GJA3 gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance for GJA3 gene 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) in GJA3 gene. In addition, sequencing of the exon-intron boundaries of the GJA8 gene 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 the GJA3 in the disease etiology in both AR and AD manners. |
| topic |
congenital cataract homozygosity mapping sanger sequencing proband GJA3 gene GJA8 mutation segregation |
| url |
http://www.mdpi.com/2073-4425/9/2/112 |
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