GM02529

GM02529 Amniotic fluid-derived cell line from Amniotic fluid

Description:

MUCOLIPIDOSIS IV
MUCOLIPIN 1; MCOLN1

Affected:

Yes

Sex:

Female

Age:

19 FW (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Lysosomal Storage Diseases

Biopsy Source

Amniotic fluid

Cell Type

Amniotic fluid-derived cell line

Transformant

Untransformed

Sample Source

Amniotic fluid-derived cell line from Amniotic fluid

Race

White

Ethnicity

ASHKENAZI

Family Member

Relation to Proband

sister

Confirmation

Clinical summary/Case history

ISCN

46,XX

Species

Homo sapiens

Common Name

Human

Remarks

Ashkenazi; abnormal cytoplasmic lysosomal storage bodies; affected sib is GM02048 Fibroblast and GM02533A Lymphoid; 46,XX; 8% of cells show random chromosome loss

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis and by Chromosome Analysis

Gene

MCOLN1

Chromosomal Location

19p13.3-p13.2

Allelic Variant 1

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).

Gene

MCOLN1

Chromosomal Location

19p13.3-p13.2

Allelic Variant 2

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.

Phenotypic Data

Remarks

Ashkenazi; abnormal cytoplasmic lysosomal storage bodies; affected sib is GM02048 Fibroblast and GM02533A Lymphoid; 46,XX; 8% of cells show random chromosome loss

Publications

Edelmann L, Dong J, Desnick RJ, Kornreich R, Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population. Am J Hum Genet70(4):1023-7 2002

PubMed ID: 11845410

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