title: SHOX mutations in a family and a fetus with Langer mesomelic dwarfism.
abstract: 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 SHOX gene. Their condition is mild, with no Madelung deformity, and was originally diagnosed as hypochondroplasia (HCH). This deletion was also transmitted to a female fetus. However, unlike her carrier relatives, the ultrasound scan of the fetus and subsequent autopsy were consistent with LMD. The fetus inherited an additional Xp deletion (Xpter-Xp22.12) that also included the SHOX gene from her chromosomally normal father. This represents a unique molecular condition for LMD: the fetus is a compound heterozygote with two independent deletions, one inherited and one arising from a de novo event.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom. simon.thomas@salisbury.nhs.uk
authors.forename: N Simon
authors.initials: NS
authors.lastname: Thomas
authors.forename: Viv
authors.initials: V
authors.lastname: Maloney
authors.forename: Paul
authors.initials: P
authors.lastname: Bass
authors.forename: Varsha
authors.initials: V
authors.lastname: Mulik
authors.forename: Diana
authors.initials: D
authors.lastname: Wellesley
authors.forename: Bruce
authors.initials: B
authors.lastname: Castle
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001344:Autopsy; D019902:Chondrocytes / Q000378:metabolism; D041321:Chromosomes, Human, X; D003360:Cosmids; D004392:Dwarfism / Q000235:genetics*; D005192:Family Health; D005260:Female; D005333:Fetus / Q000002:abnormalities; D017353:Gene Deletion; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008957:Models, Genetic; D009139:Musculoskeletal Abnormalities / Q000235:genetics; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D000074122:Short Stature Homeobox Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D014157:Transcription Factors