GM20215

GM20215 LCL from B-Lymphocyte

Description:

LANGER MESOMELIC DYSPLASIA
SHORT STATURE HOMEOBOX; SHOX

Affected:

Yes

Sex:

Male

Age:

65 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

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 65.3 years: height = 127.7 cm, height SD score = -7.2, upper to lower segment ratio = 1.8, upper to lower segment z-score = 30.3, arm span = 106.2 cm, arm span z-score = -9.2, right tibial length z-score = -8.0, right radial length z-score = -5.3, fourth metacarpal z-score = 0.9; high arched palate; normal fingernails; no scoliosis; mild increased carrying angle; severe mesomelia; marked ulnar hypoplasia; hypoplastic fibulae; severe Madelung wrist deformity; fused epiphyses; subject's parents reportedly had short stature (both 157 cm); sister affected with Leri-Weill dyschondrosteosis; donor subject is hemizygous or homozygous for a 1-bp insertion of a C, ins723C, in exon 6a of the SHOX gene resulting in a frameshift that replaces the carboxy terminus with 50 novel amino acids; subject has no wildtype SHOX exon 6a. Exon duplications or deletions were not ruled out, apart from the deletions detected by FISH with a SHOX cosmid.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

SHOX

Chromosomal Location

Xpter-p22.32

Allelic Variant 1

312865.0009; LANGER MESOMELIC DYSPLASIA

Identified Mutation

1-BP INS, 723C; In a man with Langer mesomelic dysplasia (249700), Zinn et al. (2002) found a hemizygous or homozygous insertion of a C (723insC) in a stretch of 6 C's in exon 6a of the SHOX gene. The insertion causes a frameshift that replaces the C terminus with 50 novel amino acids, deleting a putative SH3 binding site. Zinn et al. (2002) concluded that the SHOXa isoform is essential for normal skeletal development.

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