Dataset Information

Mutational spectrum in a Chinese cohort with congenital cataracts.

ABSTRACT:

Background

To identify the mutational spectrum in a Chinese cohort with congenital cataracts.

Methods

Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel-based next-generation sequencing, then classified into a cohort for further mutational analysis.

Results

After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty-four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified.

Conclusion

This study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts.

SUBMITTER: Liu HL

PROVIDER: S-EPMC10496047 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutational spectrum in a Chinese cohort with congenital cataracts.

Liu Hong-Li HL Zhang Dao-Wei DW Hu Fang-Yuan FY Xu Ping P Zhang Sheng-Hai SH Wu Ji-Hong JH

Molecular genetics & genomic medicine 20230620 9

<h4>Background</h4>To identify the mutational spectrum in a Chinese cohort with congenital cataracts.<h4>Methods</h4>Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel-based next-generation sequencing, then classified into a cohort for further mutational analysis.<h4>Results</h4>After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of ...[more]

PMID: 37337769

Similar Datasets

Project description:BackgroundCongenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts.MethodsForty-two unrelated non-syndromic congenital cataract families and 112 ethnically matched controls from southeast China were recruited from the southeast of China. We employed Sanger sequencing method to discover the variants. To confirm the novel mutations, STR haplotypes were constructed to check the co-segregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools including SIFT, Polyphen2, and Human Splicing Finder. The pathogenicity of all the mutations was evaluated by the guidelines of American College of Medical Genetics and InterVar software.ResultsNo previously reported HSF4 mutations were found in all the congenital cataract families. Five novel HSF4 mutations including c.187 T > C (p.Phe63Leu), c.218G > T (p.Arg73Leu), c.233A > G (p.Tyr78Cys), IVS5 c.233-1G > A and c.314G > C (p.Ser105Thr) were identified in five unrelated families with congenital cataracts, respectively. These mutations co-segregated with all affected individuals in each family were not observed in the unaffected family members or in 112 unrelated controls. All five mutations were categorized to be the disease "pathogenic" according to ACMG guidelines and using InterVar software. Mutations in the HSF4 were responsible for 11.90% Chinese families with congenital cataracts in our cohort.ConclusionsIn the study, we identified five novel HSF4 mutations in Chinese families with congenital cataracts. Our results expand the spectrum of HSF4 mutations causing congenital cataracts, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.

Project description:PurposeTo identify mutations in crystallin genes in Chinese families with congenital cataracts.MethodsForty-two unrelated families with non-syndromic congenital cataracts were enrolled in this study. The coding exons and adjacent intronic regions of crystallin genes, including CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD and CRYGS, were analyzed with Sanger sequencing. Novel variants were further evaluated in 112 ethnically matched controls. To confirm the novel mutations, short tandem repeat (STR) haplotypes were constructed to check the cosegregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools, including Sorting Intolerant From Tolerant v5.1.1 (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Human Splicing Finder. The pathogenicity of all the mutations was evaluated according to the guidelines of the American College of Medical Genetics (ACMG) and InterVar software.ResultsSeven previously reported mutations in crystallin genes identified in ten unrelated families were associated with the congenital nuclear cataracts. Four novel mutations in crystallin genes, including c.35G>T (p.R12L) in CRYAA, c.463C>A (p.Q155K) in CRYBB2, IVS1 c.10-1G>A in CRYGC, and c.346delT (p.F116Sfsx29) in CRYGD, were identified in four unrelated families with congenital cataracts. These mutations cosegregated with all affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. All four novel mutations were categorized as disease "likely pathogenic" except IVS1 c.10-1G>A in CRYGC "pathogenic" using InterVar software in accordance with the ACMG standard. Mutations in crystallin genes were responsible for 33.33% of the Chinese families with congenital cataracts in this cohort.ConclusionsIn this study, we identified four novel mutations in crystallin genes in Chinese families with congenital cataracts. The results expand the mutational spectrum of crystallin genes, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.

Dataset Information

Mutational spectrum in a Chinese cohort with congenital cataracts.

Background

Methods

Results

Conclusion

Publications

Mutational spectrum in a Chinese cohort with congenital cataracts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets