SHOX Deficiency in a Family whith Short Stature and Léri-Weill Dyschondrosteosis (LWD) and father transmission

DEL REY, G.; ARRIAZU, M. C.; MARTINS,R. R.; ROUBICEK M.

Mar del Plata, Pcia de Buenos Aires. Argentina

Congreso; XIX Reunión Anual de la Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2007

Sociedad Latinoamericana de Endocrinología Pediátrica

The SHOX gene in the pseudoautosomal region (PAR1) is involved in many important processes. Haploinsufficiency is the molecular basis of short stature in patients with idiopathic short stature, dyschondrosteosis and Turner syndrome.In cases with microdeletions or unbalanced translocations involving PAR1 (Xp22.3;Yp11.3), microsatellites SHOX-CA, DXYS233 and DXYS234 help detecting haploinsufficiency. Objective:To report clinical, cytogenetic and molecular analyses to detect SHOX deletion in a family with father and 3 children exhibiting variable expression of LWD. Methods:Family report:1st daughter, age 18, has typical features of LWD: short stature, Madelung deformity, cubitus valgus, genu varum. 2nd daughter, 15.5 y, and son, 9.75 y, have normal stature and very mild other features.Father´s height is -1 SD; he has typical features of LWD. Studies:Chromosome analysis by GTG banding, high resolution and FISH with Kal probe that maps proximally to SHOX (Xp22.3) were carried out on lymphocytes. DNA was used for PCR amplification of DXYS233, DXYS234 and  SHOX-CA. Amplification products were purified and analysed using AB1 PRISM377. Results:Cytogenetics showed normal chromosome constitution in all. All 3 siblings and their father presented microdeletion of SHOX, hemizygosis at DXYS233 and SHOX-CA, and heterozygosis at DXYS234. The deletion in the boy may be explained by paternal meiotic recombination event. We emphasize the usefulness of intragenic microsatellite markers to detect SHOX haploinsufficiency in patients with short stature and markedly variable clinical expression of LWD.