A novel de novo TP63 mutation in whole ‐exome sequencing of a Syrian family with Oral cleft and ectrodactyly

ConclusionTP63 mutations are associated with multiple autosomal dominant orofacial clefting and limb malformation disorders. The p.Arg319Leu mutation seen in this patient is de novo but also novel. Two known mutations in the same codon (c.956G  >  A, p.(Arg319His; rs121908839, c.955C >  T), p.Arg319Cys) cause ectrodactyly, providing evidence that mutating this codon is deleterious. While thisTP63 mutation is the best candidate for the patient's clinical presentation, whether it is responsible for the entire phenotype is unclear. Generation and characterization oftp63 knockout zebrafish showed necrosis and rupture of the head at 3  days post-fertilization (dpf). The embryonic phenotype could not be rescued by injection of zebrafish or human messenger RNA (mRNA). Further functional analysis is needed to determine what proportion of the phenotype is due to this mutation.

Source: Molecular Genetics & Genomic Medicine - April 18, 2023 Category: Genetics & Stem Cells Authors: Claire L. Simpson, Danielle C. Kimble, Settara C. Chandrasekharappa, NISC Comparative Sequencing Program, Khalid Alqosayer, Emily Holzinger, Blake Carrington, John McElderry, Raman Sood, Ghiath Al ‐Souqi, Hasan Albacha‐Hejazi, Joan E. Baile Tags: ORIGINAL ARTICLE Source Type: research