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Mesoaxial polydactyly is a major feature in Bardet–Biedl syndrome patients with LZTFL1 ( BBS17 ) mutations
Author(s) -
Schaefer E.,
Lauer J.,
Durand M.,
Pelletier V.,
Obringer C.,
Claussmann A.,
Braun J.J.,
Redin C.,
Mathis C.,
Muller J.,
SchmidtMutter C.,
Flori E.,
Marion V.,
Stoetzel C.,
Dollfus H.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12198
Subject(s) - polydactyly , ciliopathies , ciliopathy , bardet–biedl syndrome , missense mutation , genetics , cilium , nonsense mutation , joubert syndrome , retinitis pigmentosa , ciliogenesis , biology , mutation , medicine , gene , phenotype
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 ).