Autosomal Recessive NOTCH3-Related Leukodystrophy in Two Siblings and Review of the Literature.
Pediatr Neurol
; 148: 73-80, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37688971
ABSTRACT
BACKGROUND:
NOTCH3, a large type I transmembrane receptor expressed on arterial smooth muscle cells and capillary pericytes, features a diverse extracellular domain with 34 epidermal growth factor-like repeats. It exhibits distinct phenotypes due to variant zygosity and type; missense mutations cause CADASIL with cerebral vasculopathy, while null mutations lead to severe congenital manifestations.METHODS:
This report describes two cases with homozygous loss- of- function variants in NOTCH3 along with their clinical manifestations.RESULTS:
These patients presented with a severe congenital phenotype, including eye misalignment, visual impairment, epilepsy, global developmental delay, and subsequent development of pyramidal signs. Biallelic nonsense variants were discovered in both the cases (NM_000435.3c.2203 C > T (p. [Arg735Ter]). Livedo reticularis was not reported in our cases, although it was present in previously reported patients. Autosomal recessive NOTCH3-related leukodystrophy is usually caused by biallelic null mutations in NOTCH3.CONCLUSIONS:
The phenotype of biallelic null variants is associated with a more severe phenotype than the dominantly inherited form of the disease.
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Base de datos:
MEDLINE
Idioma:
En
Revista:
Pediatr Neurol
Asunto de la revista:
NEUROLOGIA
/
PEDIATRIA
Año:
2023
Tipo del documento:
Article