Genetic basis of galactosemia

✍ Scribed by Juergen K. V. Reichardt

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 612 KB
• Volume: 1
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380010303

✦ Synopsis

Communicated by Haig H. Kazazian, Jr.

Classic galactosemia is an inborn error of galactose metabolism and results from deficiency of the ubiquitously expressed enzyme galactose-1 -phosphate uridyltransferase (GALT). Nine missense mu. tations, three splicing mutations, three GALT protein polymorphisms, and one silent nucleotide substitution have been identified to date. Most of the disease-causing mutations are rare among patients.

The most common mutation, Q188R, has a frequency of only one-fourth in the patient population examined. Three classes of disease-causing mutations have been reported: CRM + missense mutations (the most common class), CRMmissense mutations, and splicing mutations. Thus, galactosemia is heterogeneous at the molecular level, which is noteworthy in light of the well-documented clinical variability observed in this disorder. It has also been shown that eight of nine galactosemia missense mutations occur in evolutionarily well-conserved domains, suggesting that they affect functionally and/or structurally important residues. In contrast, all protein polymorphisms alter variable amino acids which presumably are not important for the enzyme's function.