A de novo and novel nonsense variants in ASXL2 gene is associated with Shashi-Pena syndrome.

This ASXL2 gene encodes a member of a family of epigenetic regulators that bind various histone-modifying enzymes and are involved in the assembly of transcription factors at specific genomic loci. Recent research has found that pathogenic variants in ASXL2 gene can lead to Shashi-Pena syndrome. However, clinical reports of individuals with damaging ASXL2 variants were limited and clinical phenotypic information may also be incomplete at present. Here, we reported a patient from Chinese family presenting with Shashi-Pena syndrome duo to a nonsense variant c.2485C > T; p. (Gln829*) in ASXL2 and analyzed the clinical phenotypes of the patient. In addition to the typical facial appearance, feeding difficulty, cardiac dysfunction and developmental delay, the patient also demonstrated multiple clinical problems not reported in other published cases, including granulocytopenia, thrombocytopenia and "single transverse palmar crease". Additionally, this is also the first case of premature death associated to Shashi-Pena syndrome induced by ASXL2 variants in a Chinese population. Our results provided important information for genetic counseling of the family and broaden the spectrum of phenotypes and genetic variations of the syndrome.