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Genome sequencing in congenital cataracts improves diagnostic yield
Author(s) -
Ma Alan,
Grigg John R.,
Flaherty Maree,
Smith James,
Minoche Andre E.,
Cowley Mark J.,
Nash Benjamin M.,
Ho Gladys,
Gayagay Thet,
Lai Tiffany,
Farnsworth Elizabeth,
Hackett Emma L.,
Slater Katrina,
Wong Karen,
Holman Katherine J.,
Jenkins Gemma,
Cheng Anson,
Martin Frank,
Brown Natasha J.,
Leighton Sarah E.,
Amor David J.,
Goel Himanshu,
Dinger Marcel E.,
Bennetts Bruce,
Jamieson Robyn V.
Publication year - 2021
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24240
Subject(s) - exome sequencing , biology , exome , proband , genetics , dna sequencing , genome , cataracts , whole genome sequencing , personal genomics , computational biology , gene , mutation
Congenital cataracts are one of the major causes of childhood‐onset blindness around the world. Genetic diagnosis provides benefits through avoidance of unnecessary tests, surveillance of extraocular features, and genetic family information. In this study, we demonstrate the value of genome sequencing in improving diagnostic yield in congenital cataract patients and families. We applied genome sequencing to investigate 20 probands with congenital cataracts. We examined the added value of genome sequencing across a total cohort of 52 probands, including 14 unable to be diagnosed using previous microarray and exome or panel‐based approaches. Although exome or genome sequencing would have detected the variants in 35/52 (67%) of the cases, specific advantages of genome sequencing led to additional diagnoses in 10% (5/52) of the overall cohort, and we achieved an overall diagnostic rate of 77% (40/52). Specific benefits of genome sequencing were due to detection of small copy number variants (2), indels in repetitive regions (2) or single‐nucleotide variants (SNVs) in GC‐rich regions (1), not detectable on the previous microarray, exome sequencing, or panel‐based approaches. In other cases, SNVs were identified in cataract disease genes, including those newly identified since our previous study. This study highlights the additional yield of genome sequencing in congenital cataracts.