Exome Sequencing Reveals SLC4A11 Variant Underlying Congenital Hereditary Endothelial Dystrophy (CHED2) Misdiagnosed as Congenital Glaucoma

被引：3

作者：

Yousaf, Khazeema ^{[1
]}

Naz, Sadaf ^{[2
]}

Mushtaq, Asma ^{[3
,4
,5
]}

Wohler, Elizabeth ^{[6
]}

Sobreira, Nara ^{[6
]}

Ho, Bo-Man ^{[6
]}

Chen, Li-Jia ^{[5
,7
]}

Chu, Wai-Kit ^{[5
,7
]}

Bashir, Rasheeda ^{[1
]}

机构：

[1] Lahore Coll Women Univ, Dept Biotechnol, Lahore 54000, Pakistan

[2] Univ Punjab, Sch Biol Sci, Quaid i Azam Campus, Lahore 54590, Pakistan

[3] Childrens Hosp, Dept Ophthalmol, Lahore 54000, Pakistan

[4] Inst Child Hlth, Lahore 54000, Pakistan

[5] Chinese Univ Hong Kong, Hong Kong Hub Paediat Excellence, Hong Kong 999077, Peoples R China

[6] Baylor Hopkins Ctr Mendelian Genom, McKusick Nathans Dept Genet Med, Baltimore, MD 21205 USA

[7] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong 999077, Peoples R China

来源：

GENES | 2023年 / 14卷 / 02期

关键词：

congenital hereditary endothelial dystrophy; primary congenital glaucoma; intraocular pressure; PAKISTANI FAMILIES; MUTATION ANALYSIS; CYP1B1; MUTATIONS; INDIAN FAMILIES; GENE; MODEL;

D O I：

10.3390/genes14020310

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Autosomal recessive congenital hereditary endothelial dystrophy (CHED2) may be misdiagnosed as primary congenital glaucoma (PCG) due to similar clinical phenotypes during early infancy. In this study, we identified a family with CHED2, which was previously misdiagnosed as having PCG, and followed up for 9 years. Linkage analysis was first completed in eight PCG-affected families, followed by whole-exome sequencing (WES) in family PKGM3. The following in silico tools were used to predict the pathogenic effects of identified variants: I-Mutant 2.0, SIFT, Polyphen-2, PROVEAN, mutation taster and PhD-SNP. After detecting an SLC4A11 variant in one family, detailed ophthalmic examinations were performed again to confirm the diagnosis. Six out of eight families had CYP1B1 gene variants responsible for PCG. However, in family PKGM3, no variants in the known PCG genes were identified. WES identified a homozygous missense variant c.2024A>C, p.(Glu675Ala) in SLC4A11. Based on the WES findings, the affected individuals underwent detailed ophthalmic examinations and were re-diagnosed with CHED2 leading to secondary glaucoma. Our results expand the genetic spectrum of CHED2. This is the first report from Pakistan of a Glu675Ala variant with CHED2 leading to secondary glaucoma. The p.Glu675Ala variant is likely a founder mutation in the Pakistani population. Our findings suggest that genome-wide neonatal screening is worthwhile to avoid the misdiagnosis of phenotypically similar diseases such as CHED2 and PCG.

引用

页数：11