Description:
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN3
INHIBITOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B CELLS, KINASE-COMPLEX ASSOCIATED PROTEIN; IKBKAP
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
GeT-RM Samples |
| Class |
Disorders of the Nervous System |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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White
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Ethnicity
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ASHKENAZI
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Family Member
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2
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Relation to Proband
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sister
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| 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. |
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| Gene |
IKBKAP |
| Chromosomal Location |
9q31 |
| Allelic Variant 2 |
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. |
| 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. |
| 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 |
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| 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 |
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| 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 |
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