A novel variant of NOTCH2 causes skeletal fragility.

ABSTRACT: A 2-month-old female child presented with a low-trauma femoral fracture, low bone mass, bowing of long bones, loss of height of a thoracic vertebra, and Wormian bones. Exome sequencing revealed the presence of a novel heterozygous 4006G > C pG1336R mutation in exon 25 of NOTCH2 in the child and her father. In silico analysis considered the variant as likely deleterious. CRISPR/Cas9 was used to introduce the Notch2^4006G>C mutation into Notch2 to create Notch2^em1Ecan mutant mice. Homozygous Notch2^em1Ecan mutant mice were active, appeared healthy, had normal femoral length, but lower weights than controls. μCT of the distal femur revealed a 25 % decrease in trabecular bone volume, and a decrease in total, bone and marrow area, in periosteal perimeter and polar

SUBMITTER: Canalis E 

PROVIDER: S-EPMC12619066 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature