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New Huntington disease mutation arising from a paternal CAG 34 allele showing somatic length variation in serially passaged lymphoblasts
Author(s) -
Cannella Milena,
Maglione Vittorio,
Martino Tiziana,
Simonelli Maria,
Ragona Giuseppe,
Squitieri Ferdinando
Publication year - 2004
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30125
Subject(s) - lymphoblast , somatic cell , biology , genetics , genotype , allele , mutation , microbiology and biotechnology , germline mutation , gene , cell culture
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. © 2004 Wiley‐Liss, Inc.