C8orf37 is mutated in Bardet-Biedl syndrome and constitutes a locus allelic to non-syndromic retinal dystrophies.
PMID 26854863 | DOI 10.3109/13816810.2015.1066830 · Ophthalmic genetics · 2016 · View on PubMed ↗
Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| phenotype | Bardet-Biedl syndrome | “C8orf37 is mutated in Bardet-Biedl syndrome and constitutes a locus allelic to non-syndromic retinal dystrophies.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | retinal dystrophy | “Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | obesity | “Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | retinitis pigmentosa | “The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Population | “In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies.” | 0.80 | saudi_context_rules_v1 |
| variant | c.529C>T | “While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic.” | 0.95 | hgvs_regex_v1 |
| variant | p.Arg177Trp | “While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non-conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic.” | 0.95 | hgvs_regex_v1 |