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Title: A molecular and clinical study of Larsen Syndrome caused by mutations in FLNB
Authors: Bicknell, Louise S ×
Farrington-Rock, Claire
Shafeghati, Yousef
Rump, Patrick
Alanay, Yasemin
Alembik, Yves
Al-Madani, Navid
Firth, Helen
Hassan Karimi-Nejad, Mohammad
Ae Kim, Chong
Leask, Kathryn
Maisenbacher, Melissa
Moran, Ellen
Pappas, John G
Prontera, Paolo
de Ravel, Thomy
Fryns, Jean-Pierre
Sweeney, Elizabeth
Fryer, Alan
Unger, Sheila
Wilson, Louise C
Lachman, Ralph S
Rimoin, David L
Cohn, Daniel H
Krakow, Deborah
Robertson, Stephen P #
Issue Date: Feb-2007
Publisher: British Medical Association
Series Title: Journal of Medical Genetics vol:44 issue:2 pages:89-98
Abstract: INTRODUCTION: Larsen syndrome (LS) is an autosomal dominant osteochondrodysplasia characterised by large joint dislocations and craniofacial anomalies such as cleft palate and midface hypoplasia. Recently LS was shown to be caused by missense mutations or small in-frame deletions in FLNB, encoding the cytoskeletal protein filamin B. To further delineate the molecular causes of LS, 20 LS patients are characterized for mutations in FLNB and their phenotypes studied. METHODS: LS patients were ascertained and 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: In this report a group of 20 unrelated families with a clinical diagnosis of LS are identified with mutations in FLNB. 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 LS-associated FLNB mutations are heterozygous for either missense or small in-frame deletions. Three mutations are recurrent with one, 5071G>A, observed in 6/20 subjects. Despite homogeneity at the molecular level, significant inter- and intra-familial phenotypic variability is still apparent within this subgroup. 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 LS. These findings collectively define autosomal dominant LS and demonstrate clustering of causative mutations in FLNB.
ISSN: 0022-2593
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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