[start page][clinical aspects][biochemical info][genetics][therapeutic approaches]

Alpha Mannosidosis: Information for Families & Professionals

What is known about heritance and the gene coding for mannosidase?

The disease is inherited autosomal recessive which means that one of four children are affected -in average and that both sexes are likely affected. The gene is located at chromosome 19 as found by previous mapping. Until recently, little has been known about the genetic nature of mannosidosis. The correct gene sequence was first reported to the Gene Databank in June (Nilssen) and July (Moremen) in 1996 by two independent research groups. The gene contains approx. 3.300 nucleotides, called base pairs (bp), coding for about 1.100 amino acids. In 1995 Nilssen reported the first disease causing mutation in the fibroblasts from two siblings with mannosidosis in a highly inbred Palestinian family published in 1997. In these two patients, the cause of the disease is a point mutation at the gene, with the nucleotide Adenine substituted with Thymidin. This transfers the positively charged amino acid Histidin into the nonpolar aliphatic amino acid Leucine. Thus, a change in less than 1 promille of the of the amino acids is enough to cause malfunction of the enzyme. Since then, several genetic causes to the disease is found in man.

Illustration: Genetic map of mutations in Alpha Mannosidosis
Illustration: Geographic map of mutations in Alpha Mannosidosis

Are all parts of the enzyme equally important?

Tollersrud et al. has determined the amino acid sequence and enzyme structure in a number of different species. When comparing species, many of the human and the bovine mutations found are located to a highly "conserved" region of the mannosidase polypeptide for several species like man, cattle, cat, whale, bird, cod and slime mould. Conserved means that the amino acid sequence is identical in a large number of very different species. This indicates that these regions are very important for the enzyme function.

For additional information about this topic see Peeling the Onion: the Genetics of Alpha Mannosidosis.

For a detailed look at the genetic aspects of this and other Lysosomal Diseases, visit the offsite Human Genetic Disease: A Layman's Approach.

Back to Supported Disorders page	Home

Page title: Genetic Aspects of Alpha Mannosidosis
URL: http://www.mannosidosis.org/alphaman/amangene.htm
Editor: Dag Malm; Webmaster: Paul Murphy
February 11, 2001