Abstract
Purpose To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. Results The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, Conclusions We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation,
Highlights
Congenital cataract complicated by iris coloboma is not clinically common
A three-generation family with diagnosed cataract with iris coloboma was recruited for this study. e family consists of 14 individuals, including 6 males and 8 females (Figure 1). e slit lamp clinical examination of anterior segment revealed the proband (II:1) with congenital cataract accompanying iris coloboma (Figure 2)
Patients I:2, II:1, II:5, and III:1 were diagnosed as having congenital cataracts, and patients I:2, II:1, and II:5 had accompanying iris coloboma simultaneously
Summary
Congenital cataract complicated by iris coloboma is not clinically common. Congenital cataract (OMIM 604307), which is an opacification of the ocular lens present at birth [1], is usually hereditary and can be transmitted as a dominant or a recessive trait. Congenital cataract is a major cause of visual impairment and blindness worldwide, with at least a third of which being familial, and accounts for 10% of all childhood blindness [2,3,4]. Iris coloboma is most commonly inherited as an autosomal-dominant disorder [6]. It is an anatomical defect generated as a result of defective embryogenesis in ocular structures [7]. If the choroidal fissure is not completely closed at the iris, the defect will exist under the iris, and the round pupil will appear as a key hole shape known as iris coloboma. e prevalence range is approximately 1 : 64,000 to 1 : 96,000 worldwide, and approximately 1 : 100,000 in China [8]
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