Novel mutations in CRYGC are associated with congenital cataracts in Chinese families

Abstract

Congenital cataract (CC), responsible for about one-third of blindness in infants, is a major cause of vision loss in children worldwide. 10–25% of CC cases are attributed to genetic causes and CC is a clinically and genetically highly heterogeneous lens disorder in children. Autosomal dominant (AD) inheritance is the most commonly pattern. 195 unrelated non-syndromic ADCC families in this study are recruited from 15 provinces of China. Sanger sequencing approach followed by intra-familial co-segregation, in Silico analyses and interpretation of the variations according to the published guidelines of American College of Medical Genetics (ACMG), were employed to determine the genetic defects. Two mutations (p.Tyr139X and p.Ser166Phe) identified in two unrelated families were associated with their congenital nuclear cataracts and microcornea respectively, which are also reported previously. Six novel CRYGC mutations (p.Asp65ThrfsX38, p.Arg142GlyfsX5, p.Arg142AlafsX22, p.Tyr144X, p.Arg169X, and p.Tyr46Asp) were identified in other six families with congenital nuclear cataracts, respectively. Mutations in the CRYGC were responsible for 4.1% Chinese ADCC families in our cohort. Our results expand the spectrum of CRYGC mutations as well as their associated phenotypes.

Molecular Etiology of Isolated Congenital Cataract Using Next-Generation Sequencing: Single Center Exome Sequencing Data from Turkey

“…The entry for the present mutation (c.432C>G) has been also reported in ClinVar; however, there was no information regarding the phenotype. In a study by Zhong et al [2017], 8 different mutations in CRYGC including c.432C>G in a Chinese population with congenital nuclear cataract in which congenital cataract was also associated with microphthalmos similar to Case 2 were reported. Gonzalez-Huerta et al…”

PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population

“…Congenital cataract (CC) refers to a lens opacity present at birth, responsible for 10–30% of all vision loss in infants worldwide ( 3 ). In industrialized countries, the occurrence of CC is 1–6 cases per 10,000 births, whereas in China it is ~5 per 10,000 births ( 4 ).…”

Case Report: A de novo Variant of CRYGC Gene Associated With Congenital Cataract and Microphthalmia

“…To date, a total of 32 variants in CRYGC gene have been reported to be associated with congenital cataract ( Heon et al, 1999 ; Ren et al, 2000 ; Santhiya et al, 2002 ; Gonzalez-Huerta et al, 2007 ; Devi et al, 2008 ; Yao et al, 2008 ; Zhang et al, 2009 ; Kumar et al, 2011 ; Guo et al, 2012 ; Li et al, 2012 ; Kondo et al, 2013 ; Reis et al, 2013 ; Gillespie et al, 2014 ; Prokudin et al, 2014 ; Li et al, 2016 ; Ma et al, 2016 ; Patel et al, 2017 ; Sun et al, 2017 ; Zhong et al, 2017 ; Astiazaran et al, 2018 ; Li et al, 2018 ; Zhang et al, 2019 ; Zhuang et al, 2019 ; Berry et al, 2020 ; Taylan Sekeroglu et al, 2020 ; Fernandez-Alcalde et al, 2021 ; Karahan et al, 2021 ; Rechsteiner et al, 2021 ), but there were few reports about the de novo mutations. In 2017, Zhong et al reported a frameshift mutation (p.Asp65ThrfsX38) which might be de novo ( Zhong et al, 2017 ). In 2021, Rechsteiner et al reported a de novo mutation p.Glu107GlyfsX56, which causes cataracts and microphthalmia ( Rechsteiner et al, 2021 ), and Fernández-Alcalde et al reported a de novo mutation p.Leu145GlyfsX5 ( Fernandez-Alcalde et al, 2021 ).…”

“…Congenital cataract is one of the most common causes of blindness in children, with an estimated prevalence of 1–6 cases per 10,000 live births ( Santana and Waiswo, 2011 ). About 8.3%–25% of congenital cataract cases present Mendelian inheritance; autosomal dominant inheritance pattern is the most common, but autosomal recessive and X-linked patterns have also been reported ( Merin and Crawford, 1971 ; Francois, 1982 ; Zhong et al, 2017 ).…”