title: 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.affiliation: Department of Molecular Medicine, la Concepción Hospital, San German, PR 00683, USA.
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Cornier
authors.forename: Karen
authors.initials: K
authors.lastname: Staehling-Hampton
authors.forename: Kym M
authors.initials: KM
authors.lastname: Delventhal
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Caubet
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Young
authors.forename: Norman
authors.initials: N
authors.lastname: Ramirez
authors.forename: Simon E
authors.initials: SE
authors.lastname: Carlo
authors.forename: Jose
authors.initials: J
authors.lastname: Torres
authors.forename: John B
authors.initials: JB
authors.lastname: Emans
authors.forename: Peter D
authors.initials: PD
authors.lastname: Turnpenny
authors.forename: Olivier
authors.initials: O
authors.lastname: Pourquié
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004413:Dysostoses / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011647:Puerto Rico / Q000208:ethnology; D012272:Ribs / Q000002:abnormalities*; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D013904:Thoracic Vertebrae / Q000002:abnormalities*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018389:Codon, Nonsense; D004247:DNA; D017931:DNA Primers