Evidence map›Paper›PMID 38824264›Full record

ArticleMolecular biology reports2024

Distinct neurological phenotypes associated with biallelic loss of NOTCH3 function: evidence for recessive inheritance.

Behnoosh Tasharrofi, Ali Najafi, Elham Pourbakhtyaran, Susan Amirsalari, Golazin Shahbodagh Khan, Mahmoud Reza Ashrafi, Ali Reza Tavasoli, Mohammad Keramatipour, Morteza Heidari

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In one paragraph

Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Novel Mutation ofBalkan journal of medical genetics : BJMG · 2025
    Article
  2. Article
  3. Observational
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Behnoosh TasharrofiDepartment of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Ali NajafiDepartment of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Elham PourbakhtyaranDepartment of Pediatrics, Division of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Susan AmirsalariPediatric Neurology Department, New Hearing Technologies Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Golazin Shahbodagh KhanDepartment of Pediatrics, Division of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Mahmoud Reza AshrafiDepartment of Pediatrics, Division of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Ali Reza TavasoliDepartment of Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA.
Mohammad KeramatipourWatson Genetic Laboratory, North Kargar Street, Tehran, Iran. keramatipour@sina.tums.ac.ir.
Morteza HeidariDepartment of Pediatrics, Division of Pediatric Neurology, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. mortezah93@gmail.com.

Funding

National Institute for Medical Research Development 983886
6 · The paper itself

Abstract

backgroundNOTCH3 variants are known to be linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, some null NOTCH3 variants with homozygous inheritance cause neurological symptoms distinct from CADASIL. The aim of this study was to expand the clinical spectrum of this distinct condition and provide further evidence of its autosomal recessive inheritance. METHODS AND

resultsWhole exome sequencing (WES) was performed on a proband who exhibited livedo racemosa, ataxia, cognitive decline, seizures, and MRI white matter abnormalities without anterior temporal pole lesions. Segregation analysis was conducted with Sanger sequencing. WES of the proband identified a novel homozygous NOTCH3 null variant (c.2984delC). The consanguineous parents were confirmed as heterozygous variant carriers. In addition, three heterozygous NOTCH3 null variants were reported as incidental findings in three unrelated cases analyzed in our center.

conclusionThe findings of this study suggest an autosomal recessive inheritance pattern in this early-onset leukoencephalopathy, in contrast to CADASIL's dominant gain-of-function mechanism; which is a clear example of genotype-phenotype correlation. Comprehensive genetic analysis provides valuable insights into disease mechanisms and facilitates diagnosis and family planning for NOTCH3-associated neurological disorders.

Indexed as

Exome SequencingGenes, RecessivePedigreePhenotypeReceptor, Notch3AdultAllelesCADASILConsanguinityFemaleGenetic Association StudiesHeterozygoteHomozygoteHumansLoss of Function MutationMagnetic Resonance ImagingNOTCH3 protein, humanReceptor, Notch3CADASILExome sequencingInheritance patternLeukodystrophyReceptor, Notch3

Identifiers

PMID38824264

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