Description:
MUCOLIPIDOSIS IV
MUCOLIPIN 1; MCOLN1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples |
| Class |
Disorders of Carbohydrate Metabolism |
| Alternate IDs |
GM17360 [MUCOLIPIDOSIS IV] |
| 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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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| MUTATION VERIFICATION |
The gene mutation(s) in this sample have been verified by 6 laboratories. |
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| Gene |
MCOLN1 |
| Chromosomal Location |
19p13.3-p13.2 |
| Allelic Variant 1 |
605248.0001; MUCOLIPIDOSIS IV |
| Identified Mutation |
IVS3AS,A>G,-2; In 12 of 21 Ashkenazi Jewish patients with mucolipidosis IV (252650) associated with the major Ashkenazi founder haplotype defined by Slaugenhaupt et al. (Am J Hum Genet 65:773-778, 1999), Bargal et al. (Nat Genet 26:118-121, 2000) identified a homozygous A-to-G transition in the acceptor splice site of the third intron of the MCOLN1 gene. One heterozygote was found among 60 Ashkenazi normal controls; this was consistent with the estimated frequency of heterozygotes (1/50) in this population. Bassi et al. (Am J Hum Genet 67:1110-1120, 2000) identified this acceptor splice site mutation, which they designated 486-2A-G, as the major founder mutation in Ashkenazi Jewish patients. The mutation disrupted the GT-AG rule of splicing and resulted in a transcript lacking 165 bp, because of the skipping of exon 4. This caused a frameshift leading to a premature translation termination 374 bp downstream. The predicted truncated protein retained only the first 21 amino acids of the wildtype protein. |
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| Gene |
MCOLN1 |
| Chromosomal Location |
19p13.3-p13.2 |
| Allelic Variant 2 |
605248.0002; MUCOLIPIDOSIS IV |
| Identified Mutation |
6,450-BP DEL; In 1 of 21 Ashkenazi Jewish patients with mucolipidosis IV (252650) associated with the minor founder haplotype defined by Slaugenhaupt et al. (Am J Hum Genet 65:773-778, 1999), Bargal et al. (Nat Genet 26:118-121, 2000) identified a homozygous 6,450-bp deletion in the MCOLN1 gene. The deletion spanned a region from 928 bp upstream from the first exon of MCOLN1 to bp 31 of exon 7 (del EX1-EX7). |
| Remarks |
Ashkenazi; see GM02048 Fibroblast; affected sib is GM02529 Amniotic; photophobia; bilateral corneal opacities; abnormal lysosomal storage bodies; donor subject is a compound heterozygote: one allele has an A>G transition in the acceptor splice site of the third intron of the MCOLN1 gene (IVS3AS-2A>G) resulting in the skipping of exon 4; the second allele has a 6,450 bp deletion spanning a region from 928 bp upstream from the first exon to bp 31 of exon 7 (del ex1-ex7) |
| La Cognata V, Cavallaro S, Detection of Structural Variants by NGS: Revealing Missing Alleles in Lysosomal Storage Diseases Biomedicines10: 2022 |
| PubMed ID: 36009380 |
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| 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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| Hantash FM, Olson SC, Anderson B, Buller A, Chen R, Crossly B, Sun W, Strom CM, Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population The Journal of molecular diagnostics : JMD8:282-7 2006 |
| PubMed ID: 16645217 |
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| Bassi MT, Manzoni M, Monti E, Pizzo MT, Ballabio A, Borsani G, Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV. Am J Hum Genet67(5):1110-20 2000 |
| PubMed ID: 11013137 |
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| Kohn G, Livni N, Ornoy A, Sekeles E, Beyth Y, Legum C, Bach G, Cohen MM, Prenatal diagnosis of mucolipidosis IV by electron microscopy. J Pediatr90:62-6 1977 |
| PubMed ID: 830895 |
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