GM20216

GM20216 LCL from B-Lymphocyte

Description:

LANGER MESOMELIC DYSPLASIA
SHORT STATURE HOMEOBOX; SHOX

Affected:

Yes

Sex:

Female

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; anthropometric measurements at age 7.3 years: height = 93.5 cm, height SD score = -5.5, upper to lower segment ratio = 1.8, upper to lower segment z-score = 14.8, arm span = 72.0 cm, arm span z-score = -8.5, right tibial length z-score = -2.5, right radial length z-score = -6.5, fourth metacarpal z-score = -0.9; high arched palate; normal fingernails; no scoliosis; marked increased carrying angle; severe mesomelia; marked ulnar hypoplasia; hypoplastic fibulae; early radiographic signs of Madelung wrist deformity were present; bone age was 6.8 years at chronological age of 7.3 years; donor subject is a compound heterozygote: one allele has a complete deletion of one SHOX gene and a second allele has a 2-bp insertion, ins350AG, in exon 3 of the SHOX gene causing a frameshift that truncates the predicted SHOX protein after the first 13 amino acids of the homeodomain [130X]; subject's mother had Leri-Weill dyschondrosteosis and was heterozygous for the SHOX gene deletion; subject's father had borderline short stature (height -1.6 SD) and short legs and was heterozygous for the ins350AG mutation; clinically normal 6 month old sister had neither the SHOX deletion nor the ins350AG mutation.

Characterizations

Gene

SHOX

Chromosomal Location

Xpter-p22.32

Allelic Variant 1

312865.0003; LANGER MESOMELIC DYSPLASIA

Identified Mutation

DEL; In a fetus with Langer mesomelic dysplasia (249700), Belin et al. (1998) confirmed deletion of both SHOX alleles by fluorescence in situ hybridization. The mother, who had dyschondrosteosis (127300), was found to be heterozygous at this locus. Belin et al. (1998) showed that Langer mesomelic dysplasia results from homozygous mutations at the SHOX locus. Shears et al. (1998) likewise demonstrated a role for homozygous deletion involving the SHOX gene in the etiology of Langer dysplasia.

Gene

SHOX

Chromosomal Location

Xpter-p22.32

Allelic Variant 2

130X; LANGER MESOMELIC DYSPLASIA

Identified Mutation

ins350AG

Phenotypic Data

Remarks

Publications

Zinn AR, Wei F, Zhang L, Elder FF, Scott CI Jr, Marttila P, Ross JL, Complete SHOX deficiency causes Langer mesomelic dysplasia. Am J Med Genet110(2):158-63 2002

PubMed ID: 12116254