title: Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome.
abstract: Bardet-Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1-19) have been identified, of which mutations inBBS1are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet-Biedl syndrome-related renal disease attending the United Kingdom national Bardet-Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4-5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations inBBS10, mutations inBBS1associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b-5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet-Biedl syndrome and identifies risk factors to be considered in genetic counseling.
authors.affiliation: Genetics and Genomic Medicine Program, University College London Great Ormond Street Institute of Child Health, elizabeth.forsythe@ucl.ac.uk.|National Bardet-Biedl Syndrome Service, Department of Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Forsythe
authors.affiliation: National Bardet-Biedl Syndrome Service, Department of Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sparks
authors.affiliation: Genetics and Genomic Medicine Program, University College London Great Ormond Street Institute of Child Health.
authors.forename: Sunayna
authors.initials: S
authors.lastname: Best
authors.affiliation: Nephrology Unit, Queen Elizabeth II Hospital, Birmingham, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Borrows
authors.affiliation: National Bardet-Biedl Syndrome Service, Department of Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Bethan
authors.initials: B
authors.lastname: Hoskins
authors.affiliation: Nephrology Unit and.
authors.forename: Ataf
authors.initials: A
authors.lastname: Sabir
authors.affiliation: Department of Endocrinology, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: Barrett
authors.affiliation: Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, United Kingdom; and.
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.affiliation: Clinical Genetics Unit and.
authors.forename: Shehla
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: Nephrology Unit, Guy's Hospital, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldsmith
authors.affiliation: Nephrology Unit and.
authors.forename: David V
authors.initials: DV
authors.lastname: Milford
authors.affiliation: University College Hospital Center for Nephrology, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.affiliation: Nephrology Unit, Queen Elizabeth II Hospital, Birmingham, United Kingdom.
authors.forename: Lukas
authors.initials: L
authors.lastname: Foggensteiner
authors.affiliation: Genetics and Genomic Medicine Program, University College London Great Ormond Street Institute of Child Health.|National Bardet-Biedl Syndrome Service, Department of Clinical Genetics, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
mesh_terms: D000293:Adolescent; D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
keywords: ESRD; genetic renal disease; human genetics; risk factors