GM05106

GM05106 LCL from B-Lymphocyte

Description:

NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN3
INHIBITOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B CELLS, KINASE-COMPLEX ASSOCIATED PROTEIN; IKBKAP

Affected:

Yes

Sex:

Female

Age:

12 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
GeT-RM Samples

Class

Disorders of the Nervous System

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

ASHKENAZI

Family Member

Relation to Proband

sister

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; absent axon flare; no cyclic vomiting; absent lingual fungiform papillae; absent deep tendon reflexes; alacrima; kyphosis; renal complications; below 5th percentile for for height; at 5th percentile for weight; nocturnal enuresis; no corneal problems; diminished corneal reflexes; strabismus; labile blood pressure; difficulty chewing; air swallowing; poor oral coordination; chronic rhinorrhea; azotemia; donor subject is homozygous for the 2507+6T>C mutation in the IKBKAP gene; this donor splice site mutation (IVS20+6T>C) leads to deletion of exon 20 from the mRNA; one affected brother died at age 19; affected brother is GM05105; father is GM05107; mother is GM05108; unaffected siblings are GM05109, GM05110, GM05111; affected paternal cousin is GM09790.

Characterizations

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227.

MUTATION VERIFICATION

The gene mutation(s) in this sample have been verified by 6 laboratories.

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

IKBKAP

Chromosomal Location

9q31

Allelic Variant 1

603722.0001; FAMILIAL DYSAUTONOMIA

Identified Mutation

c.2204+6T>C (IVS20+6T>C); Slaugenhaupt et al. (2001) found that more than 99.5% of disease alleles causing familial dysautonomia (223900) in Ashkenazi Jewish individuals carried a donor splice site mutation (IVS20+6T-C) which leads to deletion of exon 20 from mRNA. Haplotype analyses were consistent with a common founder. Anderson et al. (2001) identified the same mutation in Ashkenazi Jewish patients with familial dysautonomia.

Gene

IKBKAP

Chromosomal Location

9q31

Allelic Variant 2

603722.0001; FAMILIAL DYSAUTONOMIA

Identified Mutation

Phenotypic Data

Remarks

Publications

Kalman L, Wilson JA, Buller A, Dixon J, Edelmann L, Geller L, Highsmith WE, Holtegaard L, Kornreich R, Rohlfs EM, Payeur TL, Sellers T, Toji L, Muralidharan K, Development of genomic DNA reference materials for genetic testing of disorders common in people of ashkenazi jewish descent The Journal of molecular diagnostics : JMD11:530-6 2009

PubMed ID: 19815695

Cuajungco MP, Leyne M, Mull J, Gill SP, Lu W, Zagzag D, Axelrod FB, Maayan C, Gusella JF, Slaugenhaupt SA, Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia American journal of human genetics72:749-58 2003

PubMed ID: 12577200

Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY, Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet68(3):753-758 2001

PubMed ID: 11179021