Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone- shaped epiphyses in hands and hips
Jazyk: | English |
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ISSN: | 0002-9297 |
Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=narcis______::c665aa1b9888701e59c51e1e7d72451c https://research.rug.nl/en/publications/db5f46aa-2c9e-40d2-a25d-5026a3360b6f |
Rights: | RESTRICTED |
Přírůstkové číslo: | edsair.narcis........c665aa1b9888701e59c51e1e7d72451c |
Autor: | Hellemans, J, Coucke, PJ, Giedion, A, De Paepe, A, Kramer, P, Beemer, F, Mortier, GR |
Přispěvatelé: | University of Groningen |
Jazyk: | angličtina |
Rok vydání: | 2003 |
Předmět: | |
Zdroj: | American Journal of Human Genetics, 72(4), 1040-1046. CELL PRESS |
ISSN: | 0002-9297 |
Popis: | Acrocapitofemoral dysplasia is a recently delineated autosomal recessive skeletal dysplasia, characterized clinically by short stature with short limbs and radiographically by cone-shaped epiphyses, mainly in hands and hips. Genome-wide homozygosity mapping in two consanguineous families linked the locus to 2q35-q36 with a maximum two-point LOD score of 8.02 at marker D2S2248. Two recombination events defined the minimal critical region between markers D2S2248 and D2S2151 (3.74 cM). Using a candidate-gene approach, we identified two missense mutations in the amino-terminal signaling domain of the gene encoding Indian hedgehog (IHH). Both affected individuals of family 1 are homozygous for a 137C-->T transition (P46L), and the three patients in family 2 are homozygous for a 569T-->C transition (V190A). The two mutant amino acids are strongly conserved and predicted to be located outside the region where brachydactyly type A-1 mutations are clustered. |
Databáze: | OpenAIRE |
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