We studied the inheritance and cellular segregation of a maternally inherited, heteroplasmic MT-ND5 mutation, m.13271T>C, previously shown to cause only exercise intolerance despite being present in multiple tissues. The mutation was present at low levels in early passage, bulk muscle culture, but on subcloning, only homoplasmic clones were found. Studies of transmission showed that the mutation expanded from very low levels in the patient's mother to higher levels in the patient, particularly skeletal muscle, but was not found in the placenta and umbilical cord blood of her child. Our study suggests that the m.13271T>C is either already strictly segregated (intercellular heteroplasmy), or moves rapidly to this state in cultured cells. Transmission studies suggest that intercellular heteroplasmy may also be present in the patient's germline. Although rapid shifts in heteroplasmic mitochondrial DNA mutations reflect a bottleneck in the female germline, complete segregation will accentuate the effects of this and further complicate genetic counseling.
© 2012 Wiley Periodicals, Inc.