title: Mesoaxial polydactyly is a major feature in Bardet-Biedl syndrome patients with LZTFL1 (BBS17) mutations.
abstract: Ciliopathies are heterogeneous disorders sharing different clinical signs due to a defect at the level of the primary cilia/centrosome complex. Postaxial polydactyly is frequently reported in ciliopathies, especially in Bardet-Biedl syndrome (BBS). Clinical features and genetic results observed in a pair of dizygotic twins with BBS are reported. The following manifestations were present: retinitis pigmentosa, bilateral insertional polydactyly, cognitive impairment and renal dysfunction. X-rays of the hands confirmed the presence of a 4th mesoaxial extra-digit with Y-shaped metacarpal bones. The sequencing of LZTFL1 identified a missense mutation (NM_020347.2: p.Leu87Pro; c.260T>C) and a nonsense mutation (p.Glu260*; c.778G>T), establishing a compound heterozygous status for the twins. A major decrease of LZTFL1 transcript and protein was observed in the patient's fibroblasts. This is the second report of LZTFL1 mutations in BBS patients confirming LZTFL1 as a BBS gene. Interestingly, the only two families reported in literature thus far with LZTFL1 mutations have in common mesoaxial polydactyly, a very uncommon feature for BBS. This special subtype of polydactyly in BBS patients is easily identified on clinical examination and prompts for priority sequencing of LZTFL1 (BBS17).
authors.affiliation: Laboratoire de Génétique Médicale, INSERM U1112, Faculté de Médecine de Strasbourg, Universitaires de Strasbourg, Strasbourg, France.
authors.forename: E
authors.initials: E
authors.lastname: Schaefer
authors.forename: J
authors.initials: J
authors.lastname: Lauer
authors.forename: M
authors.initials: M
authors.lastname: Durand
authors.forename: V
authors.initials: V
authors.lastname: Pelletier
authors.forename: C
authors.initials: C
authors.lastname: Obringer
authors.forename: A
authors.initials: A
authors.lastname: Claussmann
authors.forename: J-J
authors.initials: JJ
authors.lastname: Braun
authors.forename: C
authors.initials: C
authors.lastname: Redin
authors.forename: C
authors.initials: C
authors.lastname: Mathis
authors.forename: J
authors.initials: J
authors.lastname: Muller
authors.forename: C
authors.initials: C
authors.lastname: Schmidt-Mutter
authors.forename: E
authors.initials: E
authors.lastname: Flori
authors.forename: V
authors.initials: V
authors.lastname: Marion
authors.forename: C
authors.initials: C
authors.lastname: Stoetzel
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017689:Polydactyly / Q000235:genetics* / Q000503:physiopathology; D014034:Toes / Q000002:abnormalities* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*; D014427:Twins
chemical_list: C431701:LZTFL1 protein, human; D014157:Transcription Factors
keywords: Bardet-Biedl syndrome; LZTFL1 gene; ciliopathy; mesoaxial polydactyly