Repository NIGMS Human Genetic Cell Repository
Subcollection Heritable Diseases
Lysosomal Storage Diseases
GeT-RM Samples
Class Disorders of Carbohydrate Metabolism
Alternate IDs GM17360 [MUCOLIPIDOSIS IV]
Quantity 50 µg
Quantitation Method Please see our FAQ
Biopsy Source Peripheral vein
Cell Type B-Lymphocyte
Tissue Type Blood
Transformant Epstein-Barr Virus
Race Caucasian
Ethnicity ASHKENAZI
Family Member 1
Relation to Proband proband
Confirmation Clinical summary/Case history
Species Homo sapiens
Common Name Human
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)
IDENTIFICATION OF SPECIES OF ORIGIN Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis
 
MUTATION VERIFICATION The gene mutation(s) in this sample have been verified by 6 laboratories.
 
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.
 
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).
Remark 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)
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
 
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
 
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
 
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
View pedigree 
Split Ratio 1:2
Temperature 37 C
Percent CO2 5%
Percent O2 AMBIENT
Medium Roswell Park Memorial Institute Medium 1640 with 2mM L-glutamine or equivalent
Serum 20% fetal bovine serum Not Inactivated
Substrate None specified
Subcultivation Method dilution - add fresh medium