Lamin Gene Testing

From 2003 to december 2015 561 unrelated dcm probands were referred for genetic testing for familial dcm and 35 6 2 had a pathogenic lmna mutation comprising 18 different lmna mutations table 1.

Lamin gene testing. Laminopathy testing lmna gtr test id help each test is a specific orderable test from a particular laboratory and is assigned a unique gtr accession number. The lamin family of proteins make up the matrix and are highly conserved in evolution. Detects sequence variations in the lmna gene typical presentation. Unlike lamin c lamin a is generated in a precursor form called prelamin a.

The lmna gene encodes two main protein products lamin a and lamin c which are generated through alternative splicing. Lamin c has six unique amino acids. Lamins a and c are intermediate filament nuclear envelope proteins encoded by the lmna gene. Mutations of the lamin a c gene lmna have been identified in 8 of all dcm patients.

Family genetic screening diagnosed further 93 lmna mutation positive. During mitosis the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Dilated cardiomyopathy dcm is a severe disease of heart muscle characterized by progressive ventricular dilation and impaired systolic function and is a major cause of congestive heart failure. One region of the protein called the sterol reductase domain gives the protein sterol reductase function specifically δ14 sterol reductase function.

Different regions domains of this protein give it two distinct functions. Lamin a c mutations among patients with familial dilated cardiomyopathy. The format is gtr00000001 1 with a leading prefix gtr followed by 8 digits a period then 1 or more digits representing the version. Two isoforms lamins a and c can be created from this gene via alternative splicing.

Prelamin a and lamin c differ in structure only at the carboxyl terminus. This creates a high amount of homology between the isoforms. In laboratory tests involving cells taken from progeria patients researchers have found that the mutation responsible for hutchinson gilford progeria causes the lmna gene to produce an abnormal. Lamin a and lamin c are intermediate filaments that are identical up to the c terminal domains pmid.

Characterised by progressive conduction system disease arrhythmia and systolic impairment lamin a c heart disease is more malignant than other common dcms due to high event rates even. Mutations in lmna cause autosomal dominant severe heart disease accounting for 10 of dilated cardiomyopathy dcm. Lmna mutations have been associated with a variety of clinical syndromes including limb girdle muscular dystrophy most common charcot marie tooth disease dilated cardiomyopathy emery dreifuss muscular dystrophy lipodystrophy disorders.