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. 2002 Apr;70(4):1023-7.
doi: 10.1086/339519. Epub 2002 Feb 13.

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

Lisa Edelmann  1 , Jianli Dong, Robert J Desnick, Ruth Kornreich
Affiliations

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

Lisa Edelmann et al. Am J Hum Genet. 2002 Apr.

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.

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Figures

Figure 1
Figure 1
Multiplex PCR of the MCOLN1 gene; 2% agarose gel showing the products that result from the multiplex PCR amplification of the MCOLN1 gene with the IVS3−2A→G and 511del6434 primer pairs. Note that the 511del6434 primers amplify a product only when the deletion is present.
Figure 2
Figure 2
ASOs of the two AJ MCOLN1 mutations. Shown are autoradiographs of dot blots hybridized with the normal IVS3−2A→G ASO (left), the mutant IVS3−2A→G ASO (middle), and the 511del6434 ASO (right). PCR samples 1–95 were amplified from genomic DNAs; sample 96 is the ddH2O control. Sample 1 was amplified from the IVS3−2A→G homozygote (GM02527), sample 8 was amplified from the 511del6434 homozygote (GM02525), samples 18 and 67 were amplified from carriers of the IVS3−2A→G mutation, and sample 49 was amplified from a carrier of the 511del6434 mutation.
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References

Electronic-Database Information

    1. Genbank, http://www.ncbi.nlm.nih.gov/Genbank/ (for Homo sapiens MCOLN1, complete coding sequence [accession number AF287270])
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for MLIV [MIM 252650] and mucolipin-1 [MIM 605248])

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