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Resolution of a mispaired secondary structure intermediate could account for a novel micro‐insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease
Author(s) -
Martín MA,
Rubio JC,
García A,
Fernández MA,
Campos Y,
Krawczak M,
Cooper DN,
Arenas J
Publication year - 2001
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2001.590108.x
Subject(s) - frameshift mutation , exon , genetics , biology , mutation , gene , amino acid , mutagenesis
We report two siblings with McArdle's disease who are both compound heterozygotes for two non‐identical frameshift mutations in the PYGM gene; a previously reported 753 delA in exon 18 and a novel 387 insA/del 8 bp in exon 10. The novel mutation is predicted to result in premature termination of translation 33 amino acids downstream of the site of mutation, potentially encoding a severely truncated protein of 419 amino acids instead of 841 amino acids. The complete lack of myophosphorylase activity observed in muscle derived from one sibling suggests that this mutation has deleterious functional consequences. The underlying mechanism of mutagenesis may have been slipped mispairing mediated by the formation of a Moebius loop‐like secondary intermediate.