CMT Type 2 and LMNA gene mutations

[Guest guest]

Abstract from J Biomol Screen. 2004 Oct;9(7):625-628.

Analysis of Genetic Variations of Lamin A/C Gene (LMNA) by Denaturing

High-Performance Liquid Chromatography.

MR, ML, Mestroni L.

University of Colorado Cardiovascular Institute, Denver.

The human LMNA gene, when mutated, has been shown to cause at least 7

human diseases: dilated cardiomyopathy, Emery Dreifuss muscular

dystrophy, limb girdle muscular dystrophy, familial partial

lipodystrophy, Charcot Marie tooth disease type II, mandibuloacral

dysplasia, and Hutchinson-Gilford Progeria (OMIM #176670). This article

describes a high-throughput method for screening the human lamin A/C

(LMNA) gene for genetic mutations and sequence variation using

denaturing high-performance liquid chromatography (DHPLC). In the

present study, 76 patients with dilated cardiomyopathy were screened for

mutations using DHPLC and sequence analysis. Abnormal elution profiles

were identified and sequenced on an ABI 377 automatic sequencer.

Heterozygous LMNA mutations were detected in 8% of the affected

patients. In addition, a number of intronic and exonic single nucleotide

polymorphisms were identified. LMNA mutations are clinically relevant in

at least 6 human diseases. This study provides a protocol for

high-throughput LMNA analysis applicable both in the research and in the

clinical diagnostic setting.