HUTCHINSON-GILFORD PROGERIA SYNDROME (HGPS) WITH MITOCHONDRIAL DNA (MTDNA) HV1 CONTROL REGION MUTATIONS

Hutchinson-Gilford Progeria syndrome (HGPS) is a rare (one in 4 – 8 million) genetic disorder among infants, characterized with
premature aging. Nuclear encoded lamin A gene (LMNA) forms heterodimers with their splice variant lamin C to create filamentous
structures present in nuclear lamina. Early studies revealed that mutations in Lamin A genes are responsible for HGPS.
Mitochondrion, the key component of cellular metabolism is also an alleged candidate to have greater level of mutagenesis with aging
and several disease conditions including cancer. In this study, on the first ever Progeria male patient identified in Bangladesh, we
analyzed the mitochondrial DNA genome by direct sequencing with AB3130 Genetic Analyzer and have evaluated the genetic
characteristic of (HGPS). We report some novel mtDNA anomalies, none of which are observed in patient’s maternal relatives. We
hereby, report four mutations (16475 G-ins, 16488 A-ins, 16496 C-ins and 16505 G-ins) in the light strand (L-strand) control region of
mitochondria. Apart from these, several other mutations (T34A / T34T heterozygous, GG59AA, A97G, A287G, T334C, C335T,
G340C,) were observed in the control region (D-loop) of mitochondria. The D-loop region of mitochondria functions as control region
of regulation for both mtDNA replication and transcription. In this region both cis acting mitochondrial encoded protein and transacting
nuclear encoded proteins play indispensible roles to maintain the regular homeostasis between replication and transcription of
mtDNA. Therefore, these mutations identified in this region are expected to pave the pathway of destabilizing mtDNA maintenance
and trigger towards apoptosis and aging.