A cystic fibrosis patient with two novel mutations in mitochondrial DNA: mild disease led to delayed diagnosis of both disorders

Am J Med Genet. 2002 Nov 15;113(1):59-64. doi: 10.1002/ajmg.10767.


A 21-year-old woman who has been suspected of mitochondrial cytopathy, but negative for common mitochondrial DNA (mtDNA) point mutations and deletions, was screened for unknown mutations in the entire mitochondrial genome by temporal temperature gradient gel electrophoresis (TTGE). Her asymptomatic mother's blood DNA was also analyzed and used as a reference. Two tRNA regions showing different TTGE patterns between the proband and her mother were sequenced. Two novel mutations, G15995A in tRNA(pro) and A8326G in tRNA(lys), were revealed. These mutations are present in heteroplasmic states. They both occurred at a nucleotide position that is highly conserved throughout evolution. This patient is also a compound heterozygote for the cystic fibrosis (CF) mutations, DeltaF508 and R347P. The phenotype for R347P has been associated with mild disease. Due to the mild features of the R347P mutation in the CF transmembrane conductance regulator (CFTR) gene and the heterogeneous clinical presentation of the mtDNA disease, the patient was not definitively diagnosed until age 21. This case underscores the importance of a complete mutational analysis of the entire mitochondrial genome when a patient suspected of mitochondrial disorder is negative for common mtDNA mutations.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • DNA, Mitochondrial / genetics*
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Transfer, Lys / genetics*
  • RNA, Transfer, Pro / genetics*
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid


  • DNA, Mitochondrial
  • RNA, Transfer, Lys
  • RNA, Transfer, Pro