PHENOTYPIC VARIABILITY IN A FAMILY WITH A MITOCHONDRIAL-DNA T8993C MUTATION

Two patients are described in a family with a mitochondrial DNA T8993C point mutation. Patient 1, the proband, was a 4-year-old male, and hi s clinical features were consistent with those of Leigh syndrome, incl uding lactic acidosis, motor development delay, and symmetric basal ga nglia lesions on magnetic resonance imaging (MRI). His mental developm ent was delayed mildly, but he has not demonstrated neurologic deterio ration. Patient 2 was his maternal aunt. She developed her first neuro logic sign at 18 months of age, thereafter her development ceased and regressed. She had lost her head control and become bedridden by 4 yea rs of age and died at 20 years of age, demonstrating a more severe cli nical course than that of Patient 1, Analysis of mitochondrial DNA fro m peripheral leukocytes of Patient 1 revealed a T8993C mutation of 99% . Patient 2 was demonstrated to have the same mutation at high abundan ce (99%) in the frozen myocardium and in the formaldehyde preserved sp inal cord, with only 18% mutant mitochondrial DNA present in the forma ldehyde preserved sciatic nerve. The mother of Patient 1, who was phen otypically normal (sister of Patient 2), had 35% mutant mitochondrial DNA in peripheral leukocytes, The authors' findings suggest that T8993 C phenotypes are highly variable and that the proportion of the mutant mitochondrial DNA may vary among tissues and not correlate well with clinical severity. (C) 1998 by Elsevier Science Inc. All rights reserv ed.