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 Citations (Scopus)

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)
JournalClinical Genetics
DOIs
StateAccepted/In press - 2016

Fingerprint

Mitochondrial Diseases
Mitochondrial DNA
Lactic Acidosis
Milk
Mutation
Muscle Hypotonia
Sequence Analysis
Genes

Keywords

  • Congenital lactic acidemia
  • Early onset encephalopathy
  • FBXL4 mutations
  • Mitochondrial disorders

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Dai, H., Zhang, V. W., El-Hattab, A. W., Ficicioglu, C., Shinawi, M., Lines, M., ... Wong, L. J. (Accepted/In press). FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome. Clinical Genetics. https://doi.org/10.1111/cge.12894

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

In: Clinical Genetics, 2016.

Research output: Contribution to journalArticle

Dai, H, Zhang, VW, El-Hattab, AW, Ficicioglu, C, Shinawi, M, Lines, M, Schulze, A, Mcnutt, M, Gotway, G, Tian, X, Chen, S, Wang, J, Craigen, WJ & Wong, LJ 2016, 'FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome', Clinical Genetics. https://doi.org/10.1111/cge.12894
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. / FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome. In: Clinical Genetics. 2016.
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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.",
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AU - Shinawi, M.

AU - Lines, M.

AU - Schulze, A.

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AU - Gotway, G.

AU - Tian, X.

AU - Chen, S.

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AU - Craigen, W. J.

AU - Wong, L. J.

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