PMID- 8490625
OWN - NLM
STAT- MEDLINE
DCOM- 19930615
LR  - 20211203
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 2
IP  - 1
DP  - 1993 Jan
TI  - Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients.
PG  - 61-7
AB  - The heterogeneity of mutations causing Tay-Sachs disease in non-Jewish 
      populations requires efficient techniques allowing the simultaneous screening for 
      both known and novel mutations. beta-hexosaminidase mRNA isolated from cultured 
      fibroblasts of 19 Tay-Sachs patients (7 with adult or late onset form of the 
      disease and 12 with infantile Tay-Sachs disease) was amplified by cDNA-PCR in two 
      overlapping segments spanning the entire coding sequence. We used chemical 
      mismatch cleavage (CMC), denaturing gradient gel electrophoresis (DGGE) and 
      direct sequencing of amplified fragments displaying a cleaved product or an 
      altered melting behavior to screen the HEX A gene for mutations and to determine 
      their distribution and frequency in the non-Jewish Tay-Sachs patients. These 
      methods allowed us to identify 31 out of 38 alleles studied (82%). In addition to 
      9 previously described mutations (the 4 bp insertion in exon 11, G to A 
      transitions at codons 170, 269, 482, 499 and 504, C to T transition at codon 499 
      and 504 and a GT to AT transition at the donor site of intron 9), we have 
      identified 10 novel mutations. These include 1 donor splice site defect in intron 
      6, 8 missense mutations at non-randomly distributed conserved residues and a 2 bp 
      deletion in exon 4. These results confirm the extreme molecular heterogeneity of 
      mutations causing Tay-Sachs disease in non-Jewish population. The strategy used 
      should be profitable for identifying mutations in large genes and for diagnostic 
      purposes.
FAU - Akli, S
AU  - Akli S
AD  - Institut Cochin de Genetique Moleculaire (ICGM), Institut National de la Sante et 
      de la Recherche Medicale, U129, Paris, France.
FAU - Chomel, J C
AU  - Chomel JC
FAU - Lacorte, J M
AU  - Lacorte JM
FAU - Bachner, L
AU  - Bachner L
FAU - Kahn, A
AU  - Kahn A
FAU - Poenaru, L
AU  - Poenaru L
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - EC 3.2.1.52 (Hexosaminidase A)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
SB  - IM
EIN - Hum Mol Genet 1993 Apr;2(4):496
GS  - HEXA
MH  - Adult
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Ethnicity
MH  - Exons
MH  - Fibroblasts/enzymology
MH  - Gene Frequency
MH  - Hexosaminidase A
MH  - Humans
MH  - Infant
MH  - Introns
MH  - Jews
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - *Point Mutation
MH  - Polymerase Chain Reaction/methods
MH  - RNA, Messenger/genetics/isolation & purification
MH  - Tay-Sachs Disease/*enzymology/*genetics
MH  - beta-N-Acetylhexosaminidases/*genetics
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1093/hmg/2.1.61 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1993 Jan;2(1):61-7. doi: 10.1093/hmg/2.1.61.