Mitochondrial DNA polymerase γ mutations: an ever expanding molecular and clinical spectrum

Deficiency of DNA polymerase gamma can compromise mitochondrial DNA synthesis and has been implicated in a variety of complex autosomal recessive and autosomal dominant mitochondrial disorders, affecting both children and adults. We sequenced the exons and proximal intronic regions of the POLG gene from 2,697 independent patients and made definitive molecular diagnosis for 95 of them (3.5%). Analysis of this cohort identified 24 novel recessive mutations and 1 novel dominant mutation. The majority of POLG mutations are missense changes. Large intragenic deletions are extremely rare. The 92 patients with 2 mutant alleles exhibited a broad spectrum of clinical phenotypes. In conclusion, sequence analysis of the POLG gene should be considered as a part of routine screening for mitochondrial disorders. (By Sha Tang, http://jmg.bmj.com/content/early/2011/08/31/jmedgenet-2011-100222.abstract?papetoc )