title: Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population.
abstract: Mutations in the MCOLN1 gene cause mucolipidosis type IV (MLIV), a severely debilitating, autosomal recessive, lysosomal storage disorder. Approximately 80% of patients with MLIV are of Ashkenazi Jewish (AJ) descent, and two mutations, IVS3-2A-->G and 511del6434, account for >95% of the mutant alleles in this population. To determine the carrier frequencies of these two mutations, 2,029 anonymous, unrelated, unaffected AJ individuals from the greater New York metropolitan area were screened. A multiplex PCR method coupled with allele-specific oligonucleotide hybridization was developed, to enable large-scale screening. The frequencies of the IVS3-2A-->G and 511del6434 mutations were 0.54% and 0.25%, respectively, for a combined carrier frequency of 0.79%, or 1 in 127 individuals (95% CI 0.40%-1.17%). The addition of both AJ mutations causing this neurodegenerative disorder should be considered for prenatal carrier screening in this population.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York University, Fifth Avenue at 100th Street, New York, NY 10029, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Edelmann
authors.forename: Jianli
authors.initials: J
authors.lastname: Dong
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: Ruth
authors.initials: R
authors.lastname: Kornreich
mesh_terms: D000483:Alleles; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009519:New York City; D011296:Prenatal Diagnosis; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels
chemical_list: C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels