SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability

Autor(es)

Jorge, Alexander A. L. ^[1] ; Souza, Silvia C. ; Nishi, Miriam Y. ; Billerbeck, Ana E. ; Libório, Débora C. C. ; Kim, Chong A. ; Arnhold, Ivo J. P. ; Mendonça, Berenice B.

Afiliação do(s) autor(es)

^[1] São Paulo (Estado). Secretaria de Estado da Saúde. Hospital das Clínicas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Endocrinology; v. 66, n. 1, p. 130-135, Jan. 2007.
• Área do conhecimento: Ciências da Saúde - Medicina
• Assunto(s): Doenças do desenvolvimento ósseo Osteocondrodisplasias Transtornos do crescimento Mutação puntual Genes homeobox

Resumo

The frequency of SHOX mutations in children with idiopathic short stature (ISS) has been found to be variable. We analysed the SHOX gene in children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the phenotypic variability in patients harbouring SHOX mutations. Sixty-three ISS, nine LWD children and 21 affected relatives. SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing. None of the ISS patients presented SHOX deletions, but two (3·2%) presented heterozygous point mutations, including the novel R147H mutation. However, when ISS patients were selected by sitting height : height ratio (SH/H) for age > 2 SD, mutation frequency detection increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point mutations. Analysis of the other relatives in the families carrying SHOX mutations identified 14 children and 17 adult patients. A broad phenotypic variability was observed in all families regarding short stature severity and Madelung deformities. However, the presence of disproportional height, assessed by SH/H, was observed in all children and 82% of adult patients, being the most common feature in our patients with SHOX mutations. Patients with SHOX mutations present a broad phenotypic variability. SHOX mutations are very frequent in LWD (89%), in opposition to ISS (3·2%) in our cohort. The use of SH/H SDS as a selection criterion increases the frequency of SHOX mutation detection to 22% and should be used for selecting ISS children to undergo SHOX mutation molecular studies. (AU)

• Processo FAPESP: 02/09687-4 - Estudo in vitro da sensibilidade ao GH de crianças com baixa estatura e investigação dos efeitos dos esteróides sexuais sobre a ação do GH em um modelo celular
• Beneficiário: Alexander Augusto de Lima Jorge
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 00/14092-4 - Diagnóstico molecular das alterações do eixo GHRH-GH-IGF-I
• Beneficiário: Ivo Jorge Prado Arnhold
• Linha de fomento: Auxílio à Pesquisa - Temático