NA02527
DNA from Fibroblast
Description:
MUCOLIPIDOSIS IV
MUCOLIPIN 1; MCOLN1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Lysosomal Storage Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
| Quantity |
50 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Ethnicity
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ASHKENAZI
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
6.2 |
| Passage Frozen |
6 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| Gene |
MCOLN1 |
| Chromosomal Location |
19p13.3-p13.2 |
| Allelic Variant 1 |
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. |
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| 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. |
| Remarks |
Ashkenazi; approx 25% of control neuraminidase activity employing GD1a and GD1b gangliosides |
| Martina JA1, Puertollano R2., Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress. Journal of Biological Chemistry293:12525-12534 2018 |
| PubMed ID: 29945972 |
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| Scotto Rosato A, Montefusco S, Soldati C, Di Paola S, Capuozzo A, Monfregola J, Polishchuk E, Amabile A, Grimm C, Lombardo A, De Matteis MA, Ballabio A, Medina DL, TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKß/VPS34 pathway Nature communications10:5630 2018 |
| PubMed ID: 31822666 |
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| Cuajungco MP, Basilio LC, Silva J, Hart T, Tringali J, Chen CC, Biel M, Grimm C, Cellular zinc levels are modulated by TRPML1-TMEM163 interaction Traffic (Copenhagen, Denmark)15:1247-65 2014 |
| PubMed ID: 25130899 |
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| Xu M, Liu K, Swaroop M, Sun W, Dehdashti SJ, McKew JC, Zheng W, A phenotypic compound screening assay for lysosomal storage diseases Journal of biomolecular screening19:168-75 2013 |
| PubMed ID: 23983233 |
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| Eichelsdoerfer JL1, Evans JA, Slaugenhaupt SA, Cuajungco MP., Zinc dyshomeostasis is linked with the loss of mucolipidosis IV-associated TRPML1 ion channel. J Biol Chem285(45):34304-8 2010 |
| PubMed ID: 20864526 |
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| Hantash FM, Olson SC, Anderson B, Buller A, Chen R, Crossly B, Sun W, Strom CM, Rapid one-step carrier detection assay of mucolipidosis IV mutations in the Ashkenazi Jewish population The Journal of molecular diagnostics : JMD8:282-7 2006 |
| PubMed ID: 16645217 |
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| Soyombo AA, Tjon-Kon-Sang S, Rbaibi Y, Bashllari E, Bisceglia J, Muallem S, Kiselyov K, TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity The Journal of biological chemistry281:7294-301 2005 |
| PubMed ID: 16361256 |
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| 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 |
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| 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 |
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| Goldin E, Cooney A, Kaneski CR, Brady RO, Schiffmann R, Mucolipidosis IV consists of one complementation group. Proc Natl Acad Sci U S A96:8562-6 1999 |
| PubMed ID: 10411915 |
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| Honey NK, Miller AL, Shows TB, The mucolipidoses: identification by abnormal electrophoretic patterns of lysosomal hydrolases. Am J Med Genet9:239-53 1981 |
| PubMed ID: 7282783 |
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