Sheila Castro-Sánchez1, María Álvarez-Satta1, Marta Cortón2, Encarna Guillén3, Carmen Ayuso2, Diana Valverde1. 1. Departamento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Spain Instituto de Investigación Biomédica Ourense-Pontevedra-Vigo (IBI), Vigo, Spain. 2. Department of Genetics, IIS-Fundación Jiménez Díaz, CIBERER, Madrid, Spain. 3. Medical Genetics Unit, Pediatrics Service, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Abstract
BACKGROUND: Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy that displays retinal dystrophy, obesity, polydactyly, cognitive impairment, urogenital anomalies and renal abnormalities as primary clinical features. To date, 19 causative genes (BBS1-19) have been involved, whose mutations would explain over 80% of patients. The overlapping phenotypes among ciliopathies, in addition to the high intrafamilial and interfamilial variability in clinical presentation, further complicate the diagnosis of this syndrome. Thus, the main purpose of this study was to elucidate some genotype-phenotype trends that could be helpful to focus the molecular diagnosis of patients with BBS. METHODS: Thirty-seven families (52 cases) with mutations in BBS1 or chaperonin-like BBS genes (BBS6, BBS10, BBS12) from our Spanish cohort were enrolled. Systemic and ocular features were documented as comprehensively as possible. RESULTS: Comparing BBS1 versus chaperonin-like genes phenotypes we found more severe clinical features in the second group, since they displayed higher prevalence of all primary features, remarkable being the frequency of cognitive impairment (75%) in BBS12 and urogenital anomalies (83%) in patients with BBS10. With regards to p.(Met390Arg) cases, homozygotes showed a relatively more severe ocular phenotype than compound heterozygotes, since more severe fundus alterations and higher frequency of cataracts and dyschromatopsia (not previously described) were documented in the first group. The phenotypes observed frequently overlapped with Alström syndrome and, in the case of chaperonin-like genes, McKusick-Kauffman syndrome overlapping was detected. CONCLUSIONS: We provide the first evidence of BBS12 mutations related to severe phenotypes as previously described for patients with BBS10, while BBS1 ocular phenotype should not be considered as mild as generally reported when compared with other BBS phenotypes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND:Bardet-Biedl syndrome (BBS) is a pleiotropic autosomal recessive ciliopathy that displays retinal dystrophy, obesity, polydactyly, cognitive impairment, urogenital anomalies and renal abnormalities as primary clinical features. To date, 19 causative genes (BBS1-19) have been involved, whose mutations would explain over 80% of patients. The overlapping phenotypes among ciliopathies, in addition to the high intrafamilial and interfamilial variability in clinical presentation, further complicate the diagnosis of this syndrome. Thus, the main purpose of this study was to elucidate some genotype-phenotype trends that could be helpful to focus the molecular diagnosis of patients with BBS. METHODS: Thirty-seven families (52 cases) with mutations in BBS1 or chaperonin-like BBS genes (BBS6, BBS10, BBS12) from our Spanish cohort were enrolled. Systemic and ocular features were documented as comprehensively as possible. RESULTS: Comparing BBS1 versus chaperonin-like genes phenotypes we found more severe clinical features in the second group, since they displayed higher prevalence of all primary features, remarkable being the frequency of cognitive impairment (75%) in BBS12 and urogenital anomalies (83%) in patients with BBS10. With regards to p.(Met390Arg) cases, homozygotes showed a relatively more severe ocular phenotype than compound heterozygotes, since more severe fundus alterations and higher frequency of cataracts and dyschromatopsia (not previously described) were documented in the first group. The phenotypes observed frequently overlapped with Alström syndrome and, in the case of chaperonin-like genes, McKusick-Kauffman syndrome overlapping was detected. CONCLUSIONS: We provide the first evidence of BBS12 mutations related to severe phenotypes as previously described for patients with BBS10, while BBS1 ocular phenotype should not be considered as mild as generally reported when compared with other BBS phenotypes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Adrian Dockery; Kirk Stephenson; David Keegan; Niamh Wynne; Giuliana Silvestri; Peter Humphries; Paul F Kenna; Matthew Carrigan; G Jane Farrar Journal: Genes (Basel) Date: 2017-11-03 Impact factor: 4.096
Authors: William B Barrell; John N Griffin; Jessica-Lily Harvey; Davide Danovi; Philip Beales; Agamemnon E Grigoriadis; Karen J Liu Journal: Front Mol Neurosci Date: 2019-06-21 Impact factor: 5.639