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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.

SUBMITTER: Edelmann L

PROVIDER: S-EPMC379096 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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Carrier screening for mucolipidosis type IV in the American Ashkenazi Jewish population.

Edelmann Lisa L Dong Jianli J Desnick Robert J RJ Kornreich Ruth R

American journal of human genetics 20020213 4

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 m ...[more]

PMID: 11845410

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Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population.

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| S-EPMC1867596 | biostudies-literature

Beyond the "Jewish panel": the importance of offering expanded carrier screening to the Ashkenazi Jewish population.

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2010-08-16 | GSE23636 | GEO

Expanded genetic screening panel for the Ashkenazi Jewish population.

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Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases.

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2010-08-16 | E-GEOD-23636 | biostudies-arrayexpress

Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants.

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Lessons learned from expanded reproductive carrier screening in self-reported Ashkenazi, Sephardi, and Mizrahi Jewish patients.

Project description:BACKGROUND:Next-generation sequencing (NGS)-based panels have gained traction as a strategy for reproductive carrier screening. Their value for screening Ashkenazi Jewish (AJ) individuals, who have benefited greatly from population-wide targeted testing, as well as Sephardi/Mizrahi Jewish (SMJ) individuals (an underserved population), has not been fully explored. METHODS:The clinical utilization by 6,805 self-reported Jewish individuals of an expanded NGS panel, along with several ancillary assays, was assessed retrospectively. Data were extracted for a subset of 96 diseases that, during the panel design phase, were classified as being AJ-, SMJ-, or pan-Jewish/pan-ethnic-relevant. RESULTS:64.6% of individuals were identified as carriers of one or more of these 96 diseases. Over 80% of the reported variants would have been missed by following recommended AJ screening guidelines. 10.7% of variants reported for AJs were in "SMJ-relevant genes," and 31.2% reported for SMJs were in "AJ-relevant genes." Roughly 2.5% of individuals carried a novel, likely pathogenic variant. One in 16 linked cohort couples was identified as a carrier couple for at least one of these 96 diseases. CONCLUSION:For maximal carrier identification, this study supports using expanded NGS panels for individuals of all Jewish backgrounds. This approach can better empower at-risk couples for reproductive decision making.

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