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Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population
- Source :
- Human mutation. 17(5)
- Publication Year :
- 2001
-
Abstract
- The gene MCOLN1 is mutated in Mucolipidosis type IV (MLIV), a neurodegenerative, recessive, lysosomal storage disorder. The disease is found in relatively high frequency among Ashkenazi Jews due to two founder mutations that comprise 95% of the MLIV alleles in this population [Bargal et al., 2000]. In this report we complete the mutation analysis of Jewish and non-Jewish MLIV patients whose DNA were available to us. Four novel mutations were identified in the MCOLN1 gene of severely affected patients: two missense, T232P and F465L; a nonsense, R322X; and an 11-bp insertion in exon 12. The nonsense mutation (R322X) was identified in two unrelated patients with different haplotypes in the MCOLN1 chromosomal region, indicating a mutation hotspot in this CpG site. An in-frame deletion (F408del) was identified in a patient with unusual mild psychomotor retardation. The frequency of MLIV in the general Jewish Ashkenazi population was estimated in a sample of 2,000 anonymous, unrelated individuals assayed for the two founder mutations. This analysis indicated a heterozygotes frequency of about 1/100. A preferred nucleotide numbering system for MCOLN1 mutations is presented and the issue of a screening program for the detection of high-risk families in the Jewish Ashkenazi population is discussed. Hum Mutat 17:397–402, 2001. © 2001 Wiley-Liss, Inc.
- Subjects :
- Heterozygote
Nonsense mutation
Population
DNA Mutational Analysis
Molecular Sequence Data
Mutation, Missense
TRPM Cation Channels
Biology
medicine.disease_cause
Polymerase Chain Reaction
White People
Transient Receptor Potential Channels
Gene Frequency
Mucolipidoses
Genetics
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Genetic Testing
education
Genetics (clinical)
DNA Primers
Mutation
education.field_of_study
Haplotype
Membrane Proteins
Exons
medicine.disease
Ashkenazi jews
Founder Effect
Mutagenesis, Insertional
Haplotypes
Codon, Nonsense
Jews
Chromosomal region
CpG Islands
Mucolipidosis type IV
Subjects
Details
- ISSN :
- 10981004
- Volume :
- 17
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Human mutation
- Accession number :
- edsair.doi.dedup.....0e987055971bbdf46e91adaddabf08b6