FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome

H. Dai, V. W. Zhang, A. W. El-Hattab, C. Ficicioglu, M. Shinawi, M. Lines, A. Schulze, M. Mcnutt, G. Gotway, X. Tian, S. Chen, J. Wang, W. J. Craigen, L. J. Wong

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis.

Original languageEnglish (US)
Pages (from-to)634-639
Number of pages6
JournalClinical Genetics
Volume91
Issue number4
DOIs
StatePublished - Apr 1 2017

Keywords

  • FBXL4 mutations
  • congenital lactic acidemia
  • early onset encephalopathy
  • mitochondrial disorders

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome'. Together they form a unique fingerprint.

  • Cite this

    Dai, H., Zhang, V. W., El-Hattab, A. W., Ficicioglu, C., Shinawi, M., Lines, M., Schulze, A., Mcnutt, M., Gotway, G., Tian, X., Chen, S., Wang, J., Craigen, W. J., & Wong, L. J. (2017). FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome. Clinical Genetics, 91(4), 634-639. https://doi.org/10.1111/cge.12894