Skeletal dysplasia

Gene: NOTCH1

Green List (high evidence)

PMID: 35947102:
- Seven unrelated patients with leukoencephalopathy and calcifications, germline heterozygous de novo gain-of-function variants in NOTCH1.
- Other clinical features include intellectual disability, spasticity and etc. Childhood onset in most individuals however 15y and 40y reported in two individuals.
- Missense and small inframe insertion variants in the negative regulatory region.

Created: 1 Sep 2022, 6:27 a.m. | Last Modified: 1 Sep 2022, 6:45 a.m.

Panel Version: 1.276

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Genetic cerebral small vessel disease (MONDO:0018787), NOTCH1-related

Publications

• 35947102

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Monoallelic NOTCH1 variants identified in >10 families with Adams-Oliver syndrome, defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). Congenital heart defects have been estimated to be present in 20% of individuals with AOS; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot.

ClinGen – Limited evidence for familial thoracic aortic aneurysm and aortic dissection.

Created: 23 Mar 2022, 10:26 p.m. | Last Modified: 23 Mar 2022, 10:26 p.m.

Panel Version: 0.11860

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Adams-Oliver syndrome 5 (MIM#616028)

Publications

• 25963545
• 25132448