Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing

Itai Berger, Ziva Ben-Neriah, Talia Dor-Wolman, Avraham Shaag, Ann Saada, Shamir Zenvirt, Annick Raas-Rothschild, Michel Nadjari, Klaus H. Kaestner, Orly Elpeleg

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

The identification of disease causing mutation in patients with neurodegenerative disorders originating from small, non-consanguineous families is challenging. Three siblings were found to have ventriculomegaly at early gestation; postnatally, there was no acquisition of developmental milestones, and the muscles of the children were dystrophic. Plasma and CSF lactate levels were normal, but the activities of mitochondrial complex I and IV were markedly decreased. Using linkage analysis in the family, followed by whole exome sequencing of a single patient, we identified a pathogenic mutation in the AIFM1 gene which segregated with the disease state and was absent in 86 anonymous controls. This is the second report of a mutation in the AIFM1 gene, extending the clinical spectrum to include prenatal ventriculomegaly and underscores the importance of AIF for complex I assembly. In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families.

Original languageEnglish
Pages (from-to)517-520
Number of pages4
JournalMolecular Genetics and Metabolism
Volume104
Issue number4
DOIs
StatePublished - 1 Dec 2011
Externally publishedYes

Keywords

  • Anti-apoptotic factor
  • Complex I deficiency
  • Ventriculomegaly

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