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Identification of a novel mutation causing aspartylglucosaminuria reveals a mutation hotspot region in the aspartylglucosaminidase gene
Author(s) -
Isoniemi Annukka,
Hietala Marja,
Aula Pertti,
Jalanko Anu,
Peltonen Leena
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380050408
Subject(s) - biology , genetics , mutation , hotspot (geology) , identification (biology) , gene , computational biology , botany , geophysics , geology
Aspartylglucosaminuria (AGU) is a recessively inherited metabolic disorder caused by the deficiency of a lysosomal enzyme, aspartylglucosaminidase. The worldwide most common mutation causing the disease is the AGU Fin , enriched in Finland; all the other known AGU mutations are family‐specific. We developed exon‐specific primers to facilitate mutation search directly from the genomic DNA and identified a novel mutation, designated AGU Fin minor, in seven Finnish AGU Fin compound heterozygote patients. This deletion/frameshift mutation creates a premature translational termination codon and was shown to result in severely reduced transcript levels as quantified by the solid‐phase minisequencing method. Genealogical data on this novel mutation suggest its relatively recent introduction into the population. The AGU mutations identified so far have been reported to be evenly distributed throughout the 1 kb coding region of the AGA cDNA. We identified a mutation hotspot region of 40 bp within the 12.5 kb AGA gene containing two previously identified mutations and the novel AGU Fin minor mutation characterized in this study. © 1995 Wiley‐Liss, Inc.