2. Academic Validation
  3. Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy

Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy

  • Neurogenetics. 2016 Jul;17(3):187-90. doi: 10.1007/s10048-016-0483-3.
Ronen Spiegel 1 2,  Avraham Shaag 3,  Stavit Shalev 4 5,  Orly Elpeleg 3
Affiliations

Affiliations

  • 1 Pediatric Department B, Emek Medical Center, Afula, Israel. spiegelr@zahav.net.il.
  • 2 Rappaport faculty of Medicine, Technion, Haifa, Israel. spiegelr@zahav.net.il.
  • 3 Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 4 Genetic Institute, Emek Medical Center, Afula, Israel.
  • 5 Rappaport faculty of Medicine, Technion, Haifa, Israel.
PMID: 27122014 DOI: 10.1007/s10048-016-0483-3
Abstract

Febrile-induced neurodegenerative diseases are a heterogeneous group of genetic disorders most commonly inborn errors of metabolism that result in irreversible damage involving the central nervous system. Here, we report on five siblings of consanguineous family who developed normally for the first 6-12 months of life then presented with a severe leukoencephalopathy following a trivial febrile illness. Using homozygosity mapping followed by whole exome Sequencing, we identified a homozygous c. 281C>A mutation in the APOA1BP gene resulting in substitution of a highly conserved alanine residue with aspartic acid (p.Ala94Asp). APOA1BP encodes for epimerase that catalyzes the R to S epimerization of NAD(P)XH, a crucial step in the dehydration of these toxic metabolites accumulating during cellular metabolism. This is the first report of a defect in the nicotinamide nucleotide repair system in humans.

Keywords

APOA1BP gene; Homozygosity mapping; Leukoencephalopathy; Neurodegeneration; Nicotine amide nucleotides; Whole exome sequencing.

Figures