NA04663
DNA from Fibroblast
Description:
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN3
INHIBITOR OF KAPPA LIGHT POLYPEPTIDE GENE ENHANCER IN B CELLS, KINASE-COMPLEX ASSOCIATED PROTEIN; IKBKAP
ASPARTOACYLASE; ASPA
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of the Nervous System |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Family Member
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1
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Relation to Proband
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proband
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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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| PDL at Freeze |
5.31 |
| Passage Frozen |
7 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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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 |
ASPA |
| Chromosomal Location |
17pter-p13 |
| Allelic Variant 1 |
Y231Y; CANAVAN DISEASE SILENT POLYMORPHISM |
| Identified Mutation |
TYR231TYR; In Ashkenazi Jewish patients with Canavan disease (271900), Kaul et al. (1994) identified a 693C-A nonsense mutation in exon 5 of the ASPA gene (Y231X). They also identified a silent polymorphism, 693C/T. Expression of the mutation in COS-1 cells showed a complete loss of ASPA enzyme activity. |
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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; diagnosed within the first year of life; born at 36 weeks and small for gestational age (BW=1.69 kg); hypotonia and poor suck in neonatal period; questionable seizure in neonatal period; absent fungiform papillae on tongue; absent deep tendon reflexes; skin blotching; hyperhidrosis; alacrima; sluggish corneal reflexes; no flare response to histamine test; good linear growth; pneumonia; air swallowing; developmental delay; tongue thrusting; corneal ulcers; acrocyanosis; weak, hoarse cry; searching nystagmus when drinking; high palate; small umbilical hernia; at 25 months, BUN normal for age (5); poor coordination; constipation; vomits mucous and bile after meals; poor head control; extraneous movements and alternating low and high tone periods; no breath holding; hospitalized for diarrhea on at least one occasion; father is GM04664; mother is GM04665; 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; donor subject is also heterozygous for a silent polymorphism in the ASPA gene: 693C>T [Tyr231Tyr (Y231Y)] |
| Anderson SL, Fasih-Ahmad F, Evans AJ, Rubin BY, Carnosol, a diterpene present in rosemary, increases ELP1 levels in familial Dysautonomia (FD) patient-derived cells and healthy adults: a possible therapy for FD Human molecular genetics: 2022 |
| PubMed ID: 35708500 |
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| Even A, Morelli G, Turchetto S, Shilian M, Bail RL, Laguesse S, Krusy N, Brisker A, Brandis A, Inbar S, Chariot A, Saudou F, Dietrich P, Dragatsis I, Brone B, Broix L, Rigo JM, Weil M, Nguyen L, ATP-citrate lyase promotes axonal transport across species Nature communications12:5878 2020 |
| PubMed ID: 34620845 |
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| Gao D, Morini E, Salani M, Krauson AJ, Chekuri A, Sharma N, Ragavendran A, Erdin S, Logan EM, Li W, Dakka A, Narasimhan J, Zhao X, Naryshkin N, Trotta CR, Effenberger KA, Woll MG, Gabbeta V, Karp G, Yu Y, Johnson G, Paquette WD, Cutting GR, Talkowski ME, Slaugenhaupt SA, A deep learning approach to identify gene targets of a therapeutic for human splicing disorders Nature communications12:3332 2020 |
| PubMed ID: 34099697 |
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| Maková B, Mik V, Lišková B, Gonzalez G, Vítek D, Medvedíková M, Monfort B, Rucilová V, Kadlecová A, Khirsariya P, Gándara Barreiro Z, Havlícek L, Zatloukal M, Soural M, Paruch K, D'Autréaux B, Hajdúch M, Strnad M, Voller J, Cytoprotective activities of kinetin purine isosteres Bioorganic & medicinal chemistry33:115993 2020 |
| PubMed ID: 33497938 |
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| Bruun GH1, Bang JM1, Christensen LL1, Brøner S1, Petersen US1, Guerra B1, Grønning AG1, Doktor TK1, Andresen BS, Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells Nucleic Acids Research33:115993 2018 |
| PubMed ID: 29762696 |
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| Morini E, Gao D, Montgomery CM, Salani M, Mazzasette C, Krussig TA, Swain B, Dietrich P, Narasimhan J, Gabbeta V, Dakka A, Hedrick J, Zhao X, Weetall M, Naryshkin NA, Wojtkiewicz GG, Ko CP, Talkowski ME, Dragatsis I, Slaugenhaupt SA, ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia American journal of human genetics104:638-650 2018 |
| PubMed ID: 30905397 |
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