Consanguinity-based analysis of exome sequencing yields likely genetic causes in patients with inherited retinal dystrophy

Orphanet Journal of Rare Diseases

Yang Li¹  Zi-Bing Jin¹  Ren-Juan Shen¹  Jun-Gang Wang² 

[1] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory;Department of Ophthalmology, Eye Hospital of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences;

关键词: Inherited retinal dystrophy;    Consanguinity;    Exome sequencing;    Genetic mutation;   

DOI  :  10.1186/s13023-021-01902-5

来源: DOAJ

【 摘 要 】

Abstract Background Consanguineous families have a relatively high prevalence of genetic disorders caused by bi-allelic mutations in recessive genes. This study aims to evaluate the effectiveness and efficiency of a consanguinity-based exome sequencing approach to capturing genetic mutations in inherited retinal dystrophy families with consanguineous marriages. Methods Ten unrelated consanguineous families with a proband affected by inherited retinal dystrophy were recruited in this study. All participants underwent comprehensive ophthalmic examinations. Whole exome sequencing was performed, followed by a homozygote-prior strategy to rapidly filter disease-causing mutations. Bioinformatic prediction of pathogenicity, Sanger sequencing and co-segregation analysis were carried out for further validation. Results In ten consanguineous families, a total of 10 homozygous mutations in 8 IRD genes were identified, including 2 novel mutations, c.1654_1655delAG (p. R552Afs*5) in gene FAM161A in a patient diagnosed with retinitis pigmentosa, and c.830T > C (p.L277P) in gene CEP78 in a patient diagnosed with cone and rod dystrophy. Conclusion The genetic etiology in consanguineous families with IRD were successfully identified using consanguinity-based analysis of exome sequencing data, suggesting that this approach could provide complementary insights into genetic diagnoses in consanguineous families with variant genetic disorders.

【 授权许可】

Unknown