title: Identification of the first de novo PAR1 deletion downstream of SHOX in an individual diagnosed with Léri-Weill dyschondrosteosis (LWD).
abstract: Léri-Weill dyschondrosteosis (LWD, MIM 127300), is a dominantly inherited skeletal dysplasia with disproportionate short stature, mesomelic limb shortening, and the characteristic Madelung deformity. Two regions of the pseudoautosomal region 1 (PAR1) have been shown to be involved in LWD, SHOX (short-stature homeobox-containing gene) and the downstream enhancer region. We report our genetic findings of a young girl clinically diagnosed with LWD. We analyzed the proband and her family using MLPA and microsatellite analysis. We identified a deletion, 726-866 kb in size, of the downstream SHOX enhancer region in the proband. Neither parent carried the deletion. Microsatellite analysis showed that the deleted allele was of paternal origin. The mutation is more likely to have arisen from a de novo event but paternal gonadal mosaicism cannot be excluded. In conclusion, we report the clinical and molecular details of the first case of a de novo deletion of the downstream PAR1 region in an LWD individual. De novo deletions of SHOX and the downstream enhancer region must be therefore considered in cases of isolated LWD.
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPaz, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Barroso
authors.forename: Sara
authors.initials: S
authors.lastname: Benito-Sanz
authors.forename: Alberta
authors.initials: A
authors.lastname: Belinchón
authors.forename: Patricia
authors.initials: P
authors.lastname: Yuste-Checa
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gracia
authors.forename: Angel
authors.initials: A
authors.lastname: Aragones
authors.forename: Angel
authors.initials: A
authors.lastname: Campos-Barros
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
mesh_terms: D002648:Child; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*; D000074122:Short Stature Homeobox Protein; D013577:Syndrome
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein