Year: 2006
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Larsen syndrome is an autosomal dominant osteochondrodysplasia characterised by large-joint dislocations and craniofacial anomalies. Recently, Larsen syndrome was shown to be caused by missense mutations or small inframe deletions in FLNB, encoding the cytoskeletal protein filamin B. To further delineate the molecular causes of Larsen syndrome, 20 probands with Larsen syndrome together with their affected relatives were evaluated for mutations in FLNB and their phenotypes studied. METHODS: Probands were screened for mutations in FLNB using a combination of denaturing high-performance liquid chromatography, direct sequencing and restriction endonuclease digestion. Clinical and radiographical features of the patients were evaluated. RESULTS AND DISCUSSION: The clinical signs most frequently associated with a FLNB mutation are the presence of supernumerary carpal and tarsal bones and short, broad, spatulate distal phalanges, particularly of the thumb. All individuals with Larsen syndrome-associated FLNB mutations are heterozygous for either missense or small inframe deletions. Three mutations are recurrent, with one mutation, 5071G-->A, observed in 6 of 20 subjects. The distribution of mutations within the FLNB gene is non-random, with clusters of mutations leading to substitutions in the actin-binding domain and filamin repeats 13-17 being the most common cause of Larsen syndrome. These findings collectively define autosomal dominant Larsen syndrome and demonstrate clustering of causative mutations in FLNB.
Source: Journal of Medical Genetics
Authors: Louise S Bicknell, Claire Farrington-Rock, Yousef Shafeghati, Patrick Rump, Yasemin Alanay, Yves Alembik, Navid Al-Madani, Helen Firth, Mohammad Hassan Karimi-Nejad, Chong Ae Kim, Kathryn Leask, Melissa Maisenbacher, Ellen Moran, John G Pappas, Paolo Prontera, Thomy de Ravel, Jean-Pierre Fryns, Elizabeth Sweeney, Alan Fryer, Sheila Unger, L C Wilson, Ralph S Lachman, David L Rimoin, Daniel H Cohn, Deborah Krakow, Stephen P Robertson
Institutions: University of Otago, University of California, Los Angeles, University of Social Welfare and Rehabilitation Sciences, University Medical Center Groningen, Hacettepe University, Hôpitaux Universitaires de Strasbourg, Addenbrooke's Hospital, Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, St Mary's Hospital, University of Florida, New York University Langone Orthopedic Hospital, New York University, University of Ferrara, KU Leuven, Alder Hey Children's Hospital, University of Freiburg, Great Ormond Street Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2006078771