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Novel Tay‐Sachs disease mutations from China
Author(s) -
Akalin N.,
Shi H.P.,
Vavougios G.,
Hechtman P.,
Lo W.,
Scriver C. R.,
Mahuran D.,
Kaplan F.
Publication year - 1992
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.1380010107
Subject(s) - biology , genetics , transition (genetics) , exon , microbiology and biotechnology , mutation , proband , stop codon , point mutation , gene
We describe three HEXA mutations associated with infantile Tay‐Sachs disease (TSD) in three unrelated nonconsanguineous Chinese families. Novel mutations were found in two of these families. The third is a previously reported mutation (G→A transition at nt 1444) (Nakano et al., 1988). Direct sequencing of PCR products identified a novel insertion of an A after nt 547 in family 1. This change generates an early termination codon 6 bp downstream from the insertion site. Allele‐specific oligonucleotide hybridization confirmed homozygosity in the proband. Single strand conformational polymorphism analysis and direct sequencing of amplified exon 13 revealed a T→C transition at nt 1453 with the corresponding amino acid substitution W485R in the second family. This mutation creates an Fnu4HI restriction site. The proband is homozygous for this allele. When the site‐specific mutagenized αcDNA carrying the T→C transition at nt 1453 was expressed in COS 1 cells hexosaminidase S activity was not detectable above background. A G→A transition at nt 1444 (exon 13) corresponding to the E482K substitution was found in the third family. This mutation occurs at a CpG dinucleotide. It has been reported in an Italian TSD proband and causes defective intracellular transport of the α‐subunit from the rough endoplasmic reticulum to the Golgi apparatus. © 1992 Wiley‐Liss, Inc.