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

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.

• Authors: Alberto S Cornier, Karen Staehling-Hampton, Kym M Delventhal, Yumiko Saga, Jean-Francois Caubet, Nobuo Sasaki, Sian Ellard, Elizabeth Young, Norman Ramirez, Simon E Carlo, Jose Torres, John B Emans, Peter D Turnpenny, Olivier Pourquié
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 82 Issue 6 Pg. 1334-41 (Jun 2008) ISSN: 1537-6605 [Electronic] United States
• PMID: 18485326 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Codon, Nonsense
• DNA Primers
• DNA

Topics

• Abnormalities, Multiple (genetics)
• Amino Acid Sequence
• Base Sequence
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Codon, Nonsense
• DNA (genetics)
• DNA Primers (genetics)
• Dysostoses (genetics)
• Female
• Founder Effect
• Genes, Recessive
• Hispanic or Latino (genetics)
• Humans
• Male
• Molecular Sequence Data
• Mutation
• Mutation, Missense
• Polymorphism, Single Nucleotide
• Puerto Rico (ethnology)
• Ribs (abnormalities)
• Sequence Homology, Amino Acid
• Syndrome
• Thoracic Vertebrae (abnormalities)