Complete SHOX deficiency causes Langer mesomelic dysplasia.
The SHOX (short-stature homeobox-containing) gene encodes isoforms of a homeodomain transcription factor important in human limb development. SHOX haploinsufficiency has been implicated in three human growth disorders: Turner syndrome, idiopathic short stature, and Leri-Weill dyschondrosteosis. Langer mesomelic dysplasia is thought to be the homozygous form of dyschondrosteosis. However, complete SHOX deficiency has not been demonstrated for any postnatal patient with the classic Langer phenotype. We studied four adults and one child with Langer mesomelic dysplasia. SHOX abnormalities were detected in all five probands. One was a homozygote or hemizygote and two were compound heterozygotes. The homozygous or hemizygous mutation was in exon 6a, implying that the SHOXa isoform is essential for normal skeletal development. These findings confirm clinical inferences that Langer mesomelic dysplasia is the homozygous form of Leri-Weill dyschondrosteosis and add to our understanding of genotype/phenotype relationships in SHOX deficiency disorders.
Zinn
Andrew R
AR
McDermott Center for Human Growth and Development and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Andrew.Zinn@UTSouthwestern.edu
Wei
Fanglin
F
Zhang
Ling
L
Elder
Frederick F
FF
Scott
Charles I
CI
Marttila
Pia
P
Ross
Judith L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D000074122:Short Stature Homeobox Protein
D018076:DNA, Complementary; D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein