PHENOTYPE-GUIDED GENETIC TESTING OF PEDIATRIC INHERITED RETINAL DISEASE IN THE UNITED ARAB EMIRATES.
PMID 31725702 | DOI 10.1097/IAE.0000000000002675 · Retina (Philadelphia, Pa.) · 2020 · View on PubMed ↗
PURPOSE: Inherited retinal disease is relatively common in the Arabian Gulf, but details regarding pediatric inherited retinal disease in the region are lacking. The purpose of this study is to report the experience of a regional Ocular Genetics Service with childhood-onset inherited retinal disease in the United Arab Emirates. METHODS: Retrospective series of consecutive Emirati patients referred to the Ocular Genetics Service of Cleveland Clinic Abu Dhabi over a 3-year period (2016-2018) who were diagnosed with childhood-onset inherited retinal disease (onset before 16 years old) and underwent diagnostic genetic testing guided by clinical phenotype (single gene, next-generation panel, or exome sequencing). RESULTS: Seventy-one probands were identified (38 male and 33 females), the majority of whom were symptomatic with visual problems within the first 5 years of life. All patients had disease causing mutations in 1 of 26 retinal disease genes. Recessive disease was frequently due to homozygous mutations. The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5). Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G. Some probands had mutations in syndromic genes and were confirmed to have extraocular findings. CONCLUSION: Phenotype-guided genetic testing had a remarkable yield for this patient population. Recessive disease is often from homozygous mutations. Cone-dominated phenotypes are common. There are apparent founder mutations for several genes that could be used in a targeted genetic testing strategy. Molecular diagnosis is particularly important in affected children when inherited retinal dystrophy could be a sign of syndromic disease as proper earlier diagnosis minimizes potential extraocular morbidity.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | ABCA4 | “The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5).” | 0.98 | hgnc_dict_v1 |
| gene | KCNV2 | “The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5).” | 0.98 | hgnc_dict_v1 |
| gene | CRB1 | “The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5).” | 0.98 | hgnc_dict_v1 |
| gene | CNGA3 | “The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5).” | 0.98 | hgnc_dict_v1 |
| gene | MERTK | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.98 | hgnc_dict_v1 |
| gene | RS1 | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.98 | hgnc_dict_v1 |
| phenotype | retinal dystrophy | “PHENOTYPE-GUIDED GENETIC TESTING OF PEDIATRIC INHERITED RETINAL DISEASE IN THE UNITED ARAB EMIRATES.” | 0.93 | phenotype_alias_lexicon_v2 |
| variant | p.Gly1961Glu | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.95 | hgvs_regex_v1 |
| variant | p.Leu857Pro | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.95 | hgvs_regex_v1 |
| variant | p.Glu143* | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.95 | hgvs_regex_v1 |
| variant | c.52+3A>G | “Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G.” | 0.95 | hgvs_regex_v1 |