Related Experiment Video

Updated: Mar 22, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

35.0K

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

Ronen Spiegel1,2, Avraham Shaag3, Stavit Shalev4,5

  • 1Pediatric Department B, Emek Medical Center, Afula, Israel. spiegelr@zahav.net.il.

Neurogenetics
|April 29, 2016
PubMed

Insights

A genetic defect in the APOA1BP gene causes febrile-induced neurodegenerative disease in children, leading to severe leukoencephalopathy. This study identifies a novel mutation in the nicotinamide nucleotide repair system.

Area of Science:

  • Genetics
  • Neuroscience
  • Metabolism

Background:

  • Febrile-induced neurodegenerative diseases are often inborn errors of metabolism causing irreversible central nervous system damage.
  • A consanguineous family presented with five siblings exhibiting normal development for 6-12 months, followed by severe leukoencephalopathy after a febrile illness.

Purpose of the Study:

  • To identify the genetic cause of febrile-induced neurodegenerative disease in a consanguineous family.
  • To elucidate the molecular mechanism underlying this newly identified neurological disorder.

Main Methods:

  • Homozygosity mapping was employed to identify regions of shared homozygosity among affected siblings.
  • Whole exome sequencing was performed to pinpoint the causative genetic mutation.
  • Functional analysis of the identified gene and its encoded protein was conducted.

Main Results:

  • A homozygous c.281C>A mutation in the APOA1BP gene was identified, leading to a p.Ala94Asp substitution.
  • The mutation affects epimerase, an enzyme critical for NAD(P)XH dehydration and toxic metabolite clearance.
  • This represents the first reported human defect in the nicotinamide nucleotide repair system.

Conclusions:

  • A novel genetic defect in APOA1BP causes a severe, febrile-induced leukoencephalopathy.
  • Disruption of the nicotinamide nucleotide repair pathway is implicated in neurodegeneration.
  • This finding expands the spectrum of inborn errors of metabolism affecting the central nervous system.

Keywords:
APOA1BP geneHomozygosity mappingLeukoencephalopathyNeurodegenerationNicotine amide nucleotidesWhole exome sequencing

More Related Videos

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes08:56

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Published on: October 10, 2025

838
Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice12:54

Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice

Published on: May 5, 2014

29.6K

Related Concept Videos

Lethal Alleles02:41

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
19.2K
Genetic Lingo01:11

Genetic Lingo

Overview
117.1K
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
105
Epistasis Analysis01:09

Epistasis Analysis

Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
6.2K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
44.0K
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
32.3K