Abstract
The GM2-gangliosidosis B1 variant occurs at an exceptionally high frequency in the northern part of Portugal. In most patients, the disease manifests itself as a juvenile form, as opposed to the late-infantile form described for many patients from other parts of the world. We have analyzed the beta-hexosaminidase alpha gene in 11 patients, as well as in some relatives, in order to characterize the underlying abnormalities. They were screened for the two previously identified mutations responsible for the B1 variant phenotype (G533----A, also designated as the "DN allele," and C532---T) by PCR amplification of an 800-bp DNA fragment and subsequent dot-blot hybridization with allele-specific oligonucleotides. The fragment amplified from one patient was also subcloned and sequenced. Ten patients, constituting a clinically and biochemically homogeneous group, were found to be homozygous for the DN allele. The other, whose clinical profile more resembled the late-infantile phenotype often described in the literature, was a compound heterozygote carrying the DN allele and another, as yet unidentified, abnormal allele. Our results, corroborated by previously published data, suggest that homozygotes and compound heterozygotes for the DN allele may be distinguishable at the phenotypic level, depending on the nature of the abnormality in the other allele. A common ancestral origin for the DN allele can also be postulated.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kytzia H. J., Hinrichs U., Maire I., Suzuki K., Sandhoff K. Variant of GM2-gangliosidosis with hexosaminidase A having a severely changed substrate specificity. EMBO J. 1983;2(7):1201–1205. doi: 10.1002/j.1460-2075.1983.tb01567.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maia M., Alves D., Ribeiro G., Pinto R., Sa Miranda M. C. Juvenile GM2 gangliosidosis variant B1: clinical and biochemical study in seven patients. Neuropediatrics. 1990 Feb;21(1):18–23. doi: 10.1055/s-2008-1071451. [DOI] [PubMed] [Google Scholar]
- Ohno K., Suzuki K. Mutation in GM2-gangliosidosis B1 variant. J Neurochem. 1988 Jan;50(1):316–318. doi: 10.1111/j.1471-4159.1988.tb13266.x. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanaka A., Ohno K., Sandhoff K., Maire I., Kolodny E. H., Brown A., Suzuki K. GM2-gangliosidosis B1 variant: analysis of beta-hexosaminidase alpha gene abnormalities in seven patients. Am J Hum Genet. 1990 Feb;46(2):329–339. [PMC free article] [PubMed] [Google Scholar]
- Tanaka A., Ohno K., Suzuki K. GM2-gangliosidosis B1 variant: a wide geographic and ethnic distribution of the specific beta-hexosaminidase alpha chain mutation originally identified in a Puerto Rican patient. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1015–1019. doi: 10.1016/s0006-291x(88)80945-8. [DOI] [PubMed] [Google Scholar]