Abstract
Metachromatic leucodystrophy (MLD) is an autosomal recessive lysosomal storage disease resulting from a severe deficiency of arylsulphatase A. The arylsulphatase A gene is located on chromosome 22 at q13.3. An MLD patient is described who carries a common splicing mutation (“I” allele) and a de novo ring 22 deleted for the arylsulphatase A gene. The fatehr was determined to be a heterozygous carrier of the “I” allele and the mother a heterozygous carrier of the arylsulphatase A pseudodeficiency allele. The ring 22 was shown by Southern blotting to be deleted in one copy of the arylsulphatase A gene. Minisatellite analysis showed the extent of the deletion and confirmed the biparental inheritance of chromosome 22 sequences. The carrier status of the parents and the patient's 46,XX,r(22) karyotype complicated the initial diagnosis in this family. However, the causal relationship of the ring 22 and MLD have implications for the recurrence risk in this family.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ainsworth P. J., Coulter-Mackie M. B. A double mutation in exon 6 of the beta-hexosaminidase alpha subunit in a patient with the B1 variant of Tay-Sachs disease. Am J Hum Genet. 1992 Oct;51(4):802–809. [PMC free article] [PubMed] [Google Scholar]
- Arinami T., Kondo I., Hamaguchi H., Nakajima S. Multifocal meningiomas in a patient with a constitutional ring chromosome 22. J Med Genet. 1986 Apr;23(2):178–180. doi: 10.1136/jmg.23.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BAUM H., DODGSON K. S., SPENCER B. The assay of arylsulphatases A and B in human urine. Clin Chim Acta. 1959 May;4(3):453–455. doi: 10.1016/0009-8981(59)90119-6. [DOI] [PubMed] [Google Scholar]
- Budarf M. L., McDermid H. E., Sellinger B., Emanuel B. S. Isolation and regional localization of 35 unique anonymous DNA markers for human chromosome 22. Genomics. 1991 Aug;10(4):996–1002. doi: 10.1016/0888-7543(91)90190-p. [DOI] [PubMed] [Google Scholar]
- Gieselmann V., Polten A., Kreysing J., von Figura K. Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9436–9440. doi: 10.1073/pnas.86.23.9436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gieselmann V., Zlotogora J., Harris A., Wenger D. A., Morris C. P. Molecular genetics of metachromatic leukodystrophy. Hum Mutat. 1994;4(4):233–242. doi: 10.1002/humu.1380040402. [DOI] [PubMed] [Google Scholar]
- Gustavson K. H., Arancibia W., Eriksson U., Svennerholm L. Deleted ring chromosome 22 in a mentally retarded boy. Clin Genet. 1986 Apr;29(4):337–341. doi: 10.1111/j.1399-0004.1986.tb01264.x. [DOI] [PubMed] [Google Scholar]
- Hunter A. G., Ray M., Wang H. S., Thompson D. R. Phenotypic correlations in patients with ring chromosome 22. Clin Genet. 1977 Oct;12(4):239–249. doi: 10.1111/j.1399-0004.1977.tb00933.x. [DOI] [PubMed] [Google Scholar]
- Kreysing J., von Figura K., Gieselmann V. Structure of the arylsulfatase A gene. Eur J Biochem. 1990 Aug 17;191(3):627–631. doi: 10.1111/j.1432-1033.1990.tb19167.x. [DOI] [PubMed] [Google Scholar]
- Nesslinger N. J., Gorski J. L., Kurczynski T. W., Shapira S. K., Siegel-Bartelt J., Dumanski J. P., Cullen R. F., Jr, French B. N., McDermid H. E. Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3. Am J Hum Genet. 1994 Mar;54(3):464–472. [PMC free article] [PubMed] [Google Scholar]
- Penzien J. M., Kappler J., Herschkowitz N., Schuknecht B., Leinekugel P., Propping P., Tønnesen T., Lou H., Moser H., Zierz S. Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease. Am J Hum Genet. 1993 Mar;52(3):557–564. [PMC free article] [PubMed] [Google Scholar]
- Petrella R., Levine S., Wilmot P. L., Ashar K. D., Casamassima A. C., Shapiro L. R. Multiple meningiomas in a patient with constitutional ring chromosome 22. Am J Med Genet. 1993 Aug 15;47(2):184–186. doi: 10.1002/ajmg.1320470211. [DOI] [PubMed] [Google Scholar]
- Phelan M. C., Thomas G. R., Saul R. A., Rogers R. C., Taylor H. A., Wenger D. A., McDermid H. E. Cytogenetic, biochemical, and molecular analyses of a 22q13 deletion. Am J Med Genet. 1992 Jul 15;43(5):872–876. doi: 10.1002/ajmg.1320430524. [DOI] [PubMed] [Google Scholar]
- Thomas G. H. "Pseudodeficiencies" of lysosomal hydrolases. Am J Hum Genet. 1994 Jun;54(6):934–940. [PMC free article] [PubMed] [Google Scholar]
- Tommerup N., Lothe R. Constitutional ring chromosomes and tumour suppressor genes. J Med Genet. 1992 Dec;29(12):879–882. doi: 10.1136/jmg.29.12.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tommerup N., Warburg M., Gieselmann V., Hansen B. R., Koch J., Petersen G. B. Ring chromosome 22 and neurofibromatosis. Clin Genet. 1992 Oct;42(4):171–177. doi: 10.1111/j.1399-0004.1992.tb03233.x. [DOI] [PubMed] [Google Scholar]
- Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
- Zlotogora J., Furman-Shaharabani Y., Harris A., Barth M. L., von Figura K., Gieselmann V. A single origin for the most frequent mutation causing late infantile metachromatic leucodystrophy. J Med Genet. 1994 Sep;31(9):672–674. doi: 10.1136/jmg.31.9.672. [DOI] [PMC free article] [PubMed] [Google Scholar]