No genetic differences between affected and unaffected members of a German family with Leber's hereditary optic neuropathy (LHON) with respect to ten mtDNA point mutations associated with LHON

Abstract

In order to investigate possible synergistic influences of different mtDNA mutations on penetrance and severity of Leber's hereditary optic neuropathy (LHON), a large German LHON pedigree is characterized with respect to 10 different mutations associated with LHON. All members of the family carry three different mtDNA mutations (at nucleotide 4,216, 11,778 and 13,708) in a homoplasmic form, regardless of whether or not they are clinically affected. Testing for another 7 mutations reveals negative results in all family members. Hence, the variable disease expression of the family members cannot be explained by varying combinations of LHON‐associated mtDNA mutations.

Screening of mtDNA mutations in Italian LHON pedigrees

“…DNA fragments encompassing the 12 mutations studied were amplified by PCR, carried out for 35 cycles under standard conditions. Primers used were as described previously (Carducci et al 1991;Gerbitz et al 1992;Mackey et al 1993;Newman et al 1994). The amplification products were digested using the appropriate restriction enzyme according to manufacturer's instructions.…”