Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality

Arch Neurol. 2004 Jun;61(6):950-2. doi: 10.1001/archneur.61.6.950.

Abstract

Background: SCO2 is a cytochrome c oxidase (COX) assembly gene that encodes a mitochondrial inner membrane protein that probably functions as a copper transporter. Mutations in SCO2 have been associated with severe COX deficiency and early-onset fatal infantile hypertrophic cardiomyopathy, encephalopathy, and neurogenic muscle atrophy. Fetal wastage has not been described in association with mutations of SCO2.

Objective: To investigate a case of early spontaneous abortion in a family carrying mutations in SCO2.

Design: Case report. Patients Spontaneous abortion in the first trimester occurred in a woman whose first pregnancy had also resulted in a miscarriage in the first trimester and whose only child had died at 53 days of life from cardioencephalomyopathy. This child was a compound heterozygote for mutations in SCO2, and her parents were heterozygous for each mutation.

Main outcome measures: Mutations in the abortus by sequencing the SCO2 gene and confirmation of the point mutations as determined by restriction fragment length polymorphism analysis.

Results: As in the previous affected child, we found a missense mutation (E140K) and a nonsense mutation (Q53X) in the abortus.

Conclusions: The typical clinical presentation of SCO2 mutations is severe, rapidly progressive hypertrophic cardiomyopathy that presents in the neonatal period and is often associated with respiratory difficulties, metabolic acidosis, and hypotonia. The experience in this family suggests that mutations in SCO2 may also be associated with early spontaneous abortions and fetal wastage.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aborted Fetus / enzymology
  • Abortion, Spontaneous / enzymology
  • Carrier Proteins
  • DNA Mutational Analysis
  • Electron Transport Complex IV / genetics*
  • Electron Transport Complex IV / metabolism*
  • Fatal Outcome
  • Female
  • Humans
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Mutation*
  • Protein Processing, Post-Translational / genetics
  • Proteins / genetics*

Substances

  • Carrier Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Proteins
  • SCO2 protein, human
  • Electron Transport Complex IV