Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene

We report two additional unrelated individuals sharing the same sporadic ASCL1 p.(Glu127Lys) missense variant in the bHLH domain and a common phenotype with short-segment HSCR, signs of dysautonomia, and developmental delay. One has also mild CCHS without polyalanine expansion in PHOX2B, compatible with the diagnosis of Haddad syndrome. Furthermore, missense variants with homologous position in the same bHLH domain in other genes are known to cause human diseases. The description of additional individuals carrying the same variant and similar phenotype, as well as targeted functional studies, would be interesting to further evaluate the role of ASCL1 in neurocristopathies.PMID:38287449 | DOI:10.1111/cge.14485

Source: Clinical Genetics - January 30, 2024 Category: Genetics & Stem Cells Authors: Marl ène Malbos Emma Wakeling Thierry Gautier Odile Boespflug-Tanguy Louise Busby Tashunka Taylor-Miller Benjamin Dudoignon Plamen Bokov J érôme Govin Margot Grisval Ad élaïde Rega Marie-Gabrielle Mourot De Rougemont Marie-H élène Aubriot-Lorton V Source Type: research