Lamin A Mutation Progeria

The e145k progeria mutation in la c alters lamin structure and assembly inducing profound changes in nuclear architecture a reduction in b type lamin expression and premature senescence.

Lamin a mutation progeria. Some of these are located in the α helical central rod domain required for the polymerization of the nuclear lamins into higher order structures. Progeria is caused by mutations that weaken the structure of the cell nucleus making normal cell division difficult. Mutations in the lmna gene are associated with several diseases including emery dreifuss muscular dystrophy familial partial lipodystrophy limb girdle muscular dystrophy dilated cardiomyopathy charcot marie tooth disease and restrictive dermopathy a truncated version of lamin a commonly known as progerin causes hutchinson gilford progeria syndrome. The mutations activate a cryptic splice site within exon 11 of the gene thereby causing the deletion of the processing site on prelamin a.

423 may 15 2003. 4 5 15 in subsequent mutation analysis all four affected hgps family members were found to be homozygous for a g to c transversion at. 12 this results in an accumulation of progerin that is unable to. Mutations causing progeria are defective in splicing lmna mrna therefore producing abnormal lamin a protein also known as progerin.

Numerous mutations in the human a type lamin gene lmna cause the premature aging disease progeria. In contrast to the more common laδ50 progerin mutation the e145k mutation does not alter the posttranslational processing of the c terminus which. The histone mark h4k20me3 is involved in hutchinson gilford progeria syndrome caused by de novo mutations that occurs in a gene that encodes lamin a lamin a is made but isn t processed properly. Patient cells with a mutation in this domain 433g a e145k show severely lobulated nuclei a separation of the a and b type lamins.

Parents and siblings. Several enzymes are involved in the processing of its precursor prelamin a to the mature lamin a. The mutation would then result in truncated and normal mrnas in cis whereas in trans it would inhibit transcriptional processing of the normal allele acting as a dominant negative mutation. Thus in patients lamin a may not be transcribed from the normal allele c at position 1824.

In 2003 nhgri researchers together with colleagues at the progeria research foundation the new york state institute for basic research in developmental disabilities and the university of michigan discovered that hutchinson gilford progeria is caused by a tiny point mutation in a single gene known as lamin a lmna.