VACTERL with the mitochondrial np 3243 point mutation

Am J Med Genet. 1996 Apr 24;62(4):398-403. doi: 10.1002/(SICI)1096-8628(19960424)62:4<398::AID-AJMG13>3.0.CO;2-J.


The VACTERL association of vertebral, anal, cardiovascular, tracheo-esophageal, renal, and limb defects is one of the more common congenital disorders with limb deficiency arising during blastogenesis. The cause is probably heterogeneous; a molecular basis has not yet been defined. We report on a family in which a female infant with VACTERL was born in 1977 and died at age 1 month due to renal failure. Because her mother and sister later developed classical mitochondrial cytopathy associated with the A-G point mutation at nucleotide position (np) 3243 of mitochondrial (mt) DNA, we performed a molecular analysis of mt DNA in preserved kidney tissue from the VACTERL case. We discovered 100% mutant mt DNA in multicystic and 32% mutant mt DNA in normal kidney tissue. Mild deficiency of complex I respiratory chain enzyme activity was found in the mother's muscle biopsy. Other maternal relatives were healthy but had low levels of mutant mt DNA in blood. This is the first report to provide a precise molecular basis for a case of VACTERL. The differing tissue pathology depending on the percentage of mutant mt DNA suggests a causal connection between the mutation and symptoms. VACTERL, and this type of multicystic renal dysplasia, are new phenotypes for the np 3243 point mutation. The possibility of a mitochondrial disorder should be born in mind and also that VACTERL may occur as a first manifestation of a mutation that has been present for generations. This would have major implications for patient management and for genetic counselling regarding both the risk of recurrence and risk of other mitochondrial syndromes in affected families.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anal Canal / abnormalities
  • Animals
  • DNA, Mitochondrial / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Markers
  • Heart Defects, Congenital / genetics
  • Humans
  • Infant, Newborn
  • Kidney / abnormalities
  • Limb Deformities, Congenital / pathology
  • Pedigree
  • Point Mutation*
  • Renal Insufficiency / genetics
  • Tracheoesophageal Fistula / genetics
  • Vertebrates / abnormalities


  • DNA, Mitochondrial
  • Genetic Markers