Genetic counseling and prenatal diagnosis for the mitochondrial DNA mutations at nucleotide 8993

Am J Hum Genet. 1999 Aug;65(2):474-82. doi: 10.1086/302488.

Abstract

Mitochondrial genetics is complicated by heteroplasmy, or mutant load, which may be from 1%-99%, and thus may produce a gene dosage-type effect. Limited data are available for genotype/phenotype correlations in disorders caused by mtDNA mutations; therefore, prenatal diagnosis for mtDNA mutations has been hindered by an inability to predict accurately the clinical severity expected from a mutant load measured in fetal tissue. After reviewing 44 published and 12 unpublished pedigrees, we considered the possibility of prenatal diagnosis for two common mtDNA mutations at nucleotide 8993. We related the severity of symptoms to the mutant load and predicted the clinical outcome of a given mutant load. We also used the available data to generate empirical recurrence risks for genetic counseling, which may be used in conjunction with prenatal diagnosis.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Dosage*
  • Genetic Counseling*
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Molecular Sequence Data
  • Mothers
  • Mutation*
  • Pedigree
  • Phenotype
  • Prenatal Diagnosis*
  • Prognosis
  • Risk Assessment

Substances

  • DNA, Mitochondrial
  • Adenosine Triphosphatases

Associated data

  • OMIM/516060
  • OMIM/551500