title: Identification of a novel mutation confirms the implication of IFT172 (BBS20) in Bardet-Biedl syndrome.
abstract: Bardet-Biedl syndrome (BBS; MIM 209900) is a recessive heterogeneous ciliopathy characterized by retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. So far, 20 BBS genes have been identified, with the last reported ones being found in one or very few families. Whole-exome sequencing was performed in a consanguineous family in which two affected children presented typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism and cognitive impairment) without any mutation identified in known BBS genes at the time of the study. We identified a homozygous splice-site mutation (NM_015662.2: c.4428+3A>G) in both affected siblings in the last reported BBS gene, namely, Intraflagellar Transport 172 Homolog (IFT172). Familial mutation segregation was consistent with autosomal recessive inheritance. IFT172 mutations were initially reported in Jeune and Mainzer-Saldino syndromes. Recently, mutations have also been found in isolated RP and Bardet-Biedl-like ciliopathy. This is the second report of IFT172 mutations in BBS patients validating IFT172 as the twentieth BBS gene (BBS20). Moreover, another IFT gene, IFT27, was already associated with BBS, confirming the implication of IFT genes in the pathogenesis of BBS.
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.|Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Schaefer
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Scheidecker
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Geoffroy
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Megana K
authors.initials: MK
authors.lastname: Prasad
authors.affiliation: Département de Médecine translationnelle et Neurogénétique, IGBMC, CNRS UMR 7104/INSERM U964/Université de Strasbourg, Illkirch, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Redin
authors.affiliation: Service de Pédiatrie, Centre Hospitalier de Nouvelle-Calédonie, Hôpital de Magenta, Nouméa, New Caledonia New Caledonia.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Missotte
authors.affiliation: Service de Génétique Médicale, CHU de Bordeaux, Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: Département de Médecine translationnelle et Neurogénétique, IGBMC, CNRS UMR 7104/INSERM U964/Université de Strasbourg, Illkirch, France.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Chaire de Génétique Humaine, Collège de France, Illkirch, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.affiliation: Laboratoire de Génétique Médicale, Institut de Génétique Médicale d'Alsace, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.|Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020788:Bardet-Biedl Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology / Q000379:methods; D003598:Cytoskeletal Proteins; D059472:Exome; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012863:Skeleton / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C000599964:IFT172 protein, human