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Am J Hum Genet. 2008 Jun;82(6):1334-41. doi: 10.1016/j.ajhg.2008.04.014. Epub 2008 May 15.

Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome.

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1
Department of Molecular Medicine, la Concepción Hospital, San German, PR 00683, USA.

Abstract

Spondylothoracic dysostosis (STD), also known as Jarcho-Levin syndrome (JLS), is an autosomal-recessive disorder characterized by abnormal vertebral segmentation and defects affecting spine formation, with complete bilateral fusion of the ribs at the costovertebral junction producing a "crab-like" configuration of the thorax. The shortened spine and trunk can severely affect respiratory function during early childhood. The condition is prevalent in the Puerto Rican population, although it is a panethnic disorder. By sequencing a set of candidate genes involved in mouse segmentation, we identified a recessive E103X nonsense mutation in the mesoderm posterior 2 homolog (MESP2) gene in a patient, of Puerto Rican origin and from the Boston area, who had been diagnosed with STD/JLS. We then analyzed 12 Puerto Rican families with STD probands for the MESP2 E103X mutation. Ten patients were homozygous for the E103X mutation, three patients were compound heterozygous for a second nonsense mutation, E230X, or a missense mutation, L125V, which affects a conserved leucine residue within the bHLH region. Thus, all affected probands harbored the E103X mutation. Our findings suggest a founder-effect mutation in the MESP2 gene as a major cause of the classical Puerto Rican form of STD/JLS.

PMID:
18485326
PMCID:
PMC2427230
DOI:
10.1016/j.ajhg.2008.04.014
[Indexed for MEDLINE]
Free PMC Article
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