Characterization of SHOX Deletions in Léri-Weill Dyschondrosteosis (LWD) Reveals Genetic Heterogeneity and No Recombination Hotspots

SHOX point mutations and deletions in Leri-Weill dyschondrosteosis.

C Falcinelli, L Iughetti, A Percesepe, G Calabrese, F Chiarelli, M Cisternino, L De Sanctis, I Pucarelli, G Radetti, M Wasniewska, G Weber, L Stuppia, S Bernasconi, A Forabosco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...

SHOX mutations in a family and a fetus with Langer mesomelic dwarfism.

Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD) are caused by mutations in the SHOX gene. LWD results from haploinsufficiency and is dominantly inherited, while the more severe LMD results from the homozygous loss of SHOX. We describe a family and fetus with two SHOX mutations. Several relatives carry an approximately 200 kb interstitial deletion that includes the whole ...

Loss of the SHOX gene associated with Leri-Weill dyschondrosteosis in a 45,X male.

A male patient is reported with a 45,X karyotype and Leri-Weill dyschondrosteosis (LWD). FISH analysis with SHOX and SRY gene probes was carried out. One copy of both SHOX and SRY was detected in interphase nuclei, clarifying the origin of LWD and the male phenotype. Molecular results suggested that the 45,X karyotype arose through two independent events. The first occurred at paternal meiosis ...

A novel point mutation A170P in the SHOX gene defines impaired nuclear translocation as a molecular cause for Léri-Weill dyschondrosteosis and Langer dysplasia.

Cryptic intragenic deletion of the SHOX gene in a family with Léri-Weill dyschondrosteosis detected by Multiplex Ligation-Dependent Probe Amplification (MLPA).

LWD is associated to SHOX haploinsufficiency, in most cases, due to gene deletion. Generally FISH and microsatellite analysis are used to identify SHOX deletion. MLPA is a new method of detecting gene copy variation, allowing simultaneous analysis of several regions. Here we describe the presence of a SHOX intragenic deletion in a family with LWD, analyzed through different methodologies. Genom...