New Huntington disease mutation arising from a paternal CAG34 allele showing somatic length variation in serially passaged lymphoblasts.
The analysis of somatic CAG triplet variation in lymphoblastoid cell lines from subjects carrying alleles of intermediate length (IA(33CAG) and IA(34CAG)) in Huntington disease (HD) gene disclosed instability in the DNA of the person, from whom a new expansion mutation of 45 triplets originated. The triplet size increased after about 30 passages in cell cultures in lymphoblasts with the IA(34) genotype. Lymphoblasts may provide an appropriate model for studying repeat instability in subjects with poly(CAG) repeat disorders. HD shows somatic, in addition to germ-line instability, highlighting the propensity to somatic CAG variation in human cells even with repeat numbers under the expanded edge. Factors potentially cis acting with the mutation, other than those reported in this study (CCG polymorphic stretch, the deletion of the glutamic acid residue at position 2642 and the 4-codon segment between CAG and CCG polymorphisms), should be searched for and analyzed.
Cannella
Milena
M
Neurogenetics Unit IRCCS Neuromed, Pozzilli (IS), Italy.
Maglione
Vittorio
V
Martino
Tiziana
T
Simonelli
Maria
M
Ragona
Giuseppe
G
Squitieri
Ferdinando
F
D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D005192:Family Health; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D007558:Italy; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins