OBJECTIVE: 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. PATIENTS: Sixty-three ISS, nine LWD children and 21 affected relatives. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. PATIENTS: Sixty-three ISS, nine LWDchildren and 21 affected relatives. METHODS: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. RESULTS: 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%) LWDpatients 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. CONCLUSION: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.
Authors: C Vilariño-Güell; H Chai; B H Keeling; J E Young; A Rajput; T Lynch; J O Aasly; R J Uitti; Z K Wszolek; M J Farrer; S-C Lin Journal: Neurology Date: 2009-07-21 Impact factor: 9.910
Authors: M Wasniewska; G Raiola; A Nicoletti; M C Galati; M F Messina; S Mirabelli; F De Luca Journal: J Endocrinol Invest Date: 2009-07-28 Impact factor: 4.256
Authors: S W Davis; F Castinetti; L R Carvalho; B S Ellsworth; M A Potok; R H Lyons; M L Brinkmeier; L T Raetzman; P Carninci; A H Mortensen; Y Hayashizaki; I J P Arnhold; B B Mendonça; T Brue; S A Camper Journal: Mol Cell Endocrinol Date: 2009-12-16 Impact factor: 4.102