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Molecular heterogeneity of classical and duarte galactosemia: Mutation analysis by denaturing gradient gel electrophoresis
Author(s) -
GreberPlatzer S,
Guldberg P,
Scheibenreiter S,
Item C,
Schuller E,
Patel N,
Strobl W
Publication year - 1997
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/(sici)1098-1004(1997)10:1<49::aid-humu7>3.0.co;2-h
Subject(s) - galactosemia , biology , genetics , missense mutation , allele , mutation , exon , microbiology and biotechnology , point mutation , gene , galactose , biochemistry
Classical galactosemia is caused by one common missense mutation (Q188R) and by several rare mutations in the galactose‐1‐phosphate uridyltransferase ( GALT ) gene. The most common variant of GALT, the Duarte variant, occurs as two types, Duarte‐1 (D‐1) and Duarte‐2 (D‐2), both of which carry the sequence change N314D. D‐1 increases, whereas D‐2 decreases GALT activity. To study the molecular genetics of classical and Duarte galactosemia, we analyzed the GALT mutations in 30 families with classical galactosemia, in 10 families with the D‐2 variant and in 3 individuals carrying the D‐1 allele by denaturing gradient gel electrophoresis (DGGE). DGGE detected 59 of the 60 classical galactosemia alleles. Q188R accounted for 60%, K285N accounted for 28% of these alleles. Eight novel candidate galactosemia mutations were found. On all D‐2 alleles N314D occurred in cis with two intronic sequence changes, on the D‐1 alleles in cis with a neutral mutation in exon 7. We conclude that the mutations causing galactosemia are highly heterogeneous and that K285N is a second common galactosemia mutation in our population. Hum Mutat 10:49–57, 1997 © 1997 Wiley‐Liss, Inc.