Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1

被引:14
作者
Abbruzzese, C
Porrini, SC
Mariani, B
Gould, FK
Mcabney, JP
Monckton, DG
Ashizawa, T
Giacanelli, M
机构
[1] Univ Texas, Dept Neurol, Med Branch, Galveston, TX 77555 USA
[2] Azienda Osped San Camillo Forlanini, Dipartimento Medicochirurg Neurosci, Lab Istopatol Neurogenet Mol, Rome, Italy
[3] Univ Glasgow, Inst Biomed & Life Sci, Glasgow, Lanark, Scotland
[4] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA
[5] VA Med Ctr, Houston, TX USA
关键词
D O I
10.1002/ana.10304
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Myotonic dystrophy type I (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK gene on chromosome 19q13.3. We present two siblings with DM1 who each inherited a premutation allele, (CTG)(43), stably transmitted from the mother and a full-mutation allele, either (CTG)(500) or (CTG)(180), derived from a paternal protomutation allele, (CTG)(52). Small-pool polymerase chain reaction analysis showed that the (CTG)(52) repeat allele was relatively stable in somatic tissues but was highly unstable in the male germline and extremely biased toward further expansion, consistent with the high levels of anticipation observed in DM1 families. The (CTG)(43) allele showed subtle somatic instability in the mother, with maximum additions of two repeats and deletions of one repeat. Conversely, in the younger affected siblings the (CTG)(43) allele showed a high degree of somatic instability (approximately 70% mutation load), resulting in deletions reverting to the high end of the normal range (down to [CTG](33)) and additions up to the proto-mutation range (up to [CTG](64)). The difference in the somatic stability of the (CTG)(43) allele between the mother and her offspring suggests that interallelic interactions or other mechanisms in trans regulate the stability of the (CTG)(43) premutation allele.
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页码:435 / 441
页数:7
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