Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications.
Am J Hum Genet
; 84(1): 80-4, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19110212
ABSTRACT
The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.(1) Using a homozygosity mapping strategy, we located a candidate region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the candidate region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene(6). We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteocondrodisplasias
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Calcinosis
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Deformidades Congénitas de la Mano
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Receptores Mitogénicos
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Proteínas Tirosina Quinasas Receptoras
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Predisposición Genética a la Enfermedad
Límite:
Adult
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Humans
Idioma:
En
Revista:
Am J Hum Genet
Año:
2009
Tipo del documento:
Article
País de afiliación:
Israel