First, I believe it is because Hutchinson-Gilford progeria syndrome (HGPS) is a fascinating disorder. Given that it is classified as a segmental progeroid syndrome, it might provide clues to the causes of aging, in general. Second, it also adds another disease to the list of diseases caused by mutations in the gene that encodes lamin A/C proteins. The field of research concerning lamin proteins is progressing at a rapid pace today, which could also explain the number of citations.

Yes, it describes a new discovery. The paper defines the molecular basis for HGPS, which is an extremely rare genetic disorder characterized by features of premature or accelerated aging. In the paper, we showed that 19 out of 20 classical cases of HGPS were present with de novo point mutations within the same codon of the LMNA gene. The LMNA gene encodes the lamin A/C proteins and the HGPS mutations result in the activation of a cryptic splice site that removes parts of exon 11 and produces a lamin A protein with an internal deletion. With immunofluorescence and antibodies against lamin A/C on primary fibroblasts obtained from HGPS cases, we provided visual evidence of an abnormal structure of the nuclear membrane in 48% of the cells.

Our work shows that Hutchinson-Gilford progeria syndrome, a disorder with features of premature aging, is caused by a mutation in a gene called LMNA. The mutation is only present in affected individuals and is not inherited. This work suggests that the inner nuclear lamina, which is a network of proteins found just underneath the nuclear membrane, could have an impact on life span and the development of cardiac disease.

My postdoc supervisor, Dr. Francis S. Collins—the director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH)—introduced me to the disorder, and convinced me to take on the project of defining the genetic basis for this disease.