Related Experiment Video

Updated: Sep 16, 2025

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
05:12

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model

Published on: September 4, 2017

11.0K

A case of coexisting heterozygous NOTCH3 and HTRA1 mutations in cerebral small vessel disease

Masataka Yamashiro1, Daigo Yasutomi2, Yuichiro Ohya2

  • 1Department of Neurology, National Hospital Organization Okinawa Hospital, Okinawa, Japan. masataka19930706@gmail.com.

Human Genome Variation
|July 9, 2025
PubMed

Insights

This study reports a rare case of coexisting NOTCH3 and HTRA1 mutations causing hereditary cerebral small vessel disease (CSVD). The patient exhibited unique symptoms, suggesting potential synergistic effects of these combined genetic variants in CSVD.

Area of Science:

  • Neurology
  • Genetics
  • Vascular Biology

Background:

  • Hereditary cerebral small vessel diseases (CSVDs) encompass conditions like CADASIL (NOTCH3 mutations) and HTRA1-related CSVD.
  • These diseases manifest with neurological and cognitive deficits due to vascular abnormalities.

Purpose of the Study:

  • To report a unique case of a 53-year-old Japanese woman with coexisting heterozygous NOTCH3 (p.R75P) and HTRA1 (p.R166L) mutations.
  • To compare the clinical presentation with known phenotypes of NOTCH3-related CADASIL and HTRA1-related CSVD.
  • To explore the potential synergistic effects of these coexisting variants on CSVD pathogenesis.

Main Methods:

  • Clinical case presentation and detailed phenotyping.
  • Genetic analysis to identify coexisting NOTCH3 and HTRA1 mutations.
  • Literature review and comparison with previously reported CSVD cases.

Main Results:

  • The patient presented with early-onset spastic paraparesis, frequent urination, cognitive impairment, and baldness.
  • The identified mutations were NOTCH3 p.R75P and HTRA1 p.R166L, both in heterozygous state.
  • Clinical features were compared to established phenotypes, highlighting potential novel aspects due to combined mutations.

Conclusions:

  • This case highlights the complexity of hereditary CSVD with compound heterozygosity.
  • Coexisting NOTCH3 and HTRA1 mutations may lead to distinct or overlapping clinical phenotypes.
  • Further research is needed to understand the synergistic interactions of these variants in CSVD development.

More Related Videos

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

3.7K
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging09:37

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Published on: July 14, 2016

8.4K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
61
Aneurysm II: Clinical Manifestations and Diagnostic Studies01:21

Aneurysm II: Clinical Manifestations and Diagnostic Studies

Thoracic, aortic arch and abdominal aneurysms are significant vascular conditions that can present with various clinical manifestations and lead to serious complications. Understanding these manifestations and the appropriate diagnostic studies is essential for effective management and treatment.Thoracic Aortic AneurysmsThoracic aortic aneurysms often remain asymptomatic until they reach a size that impinges on adjacent structures. They typically cause deep, diffuse chest pain that radiates to...
26
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K