Neurodevelopmental Phenotype Associated with: Report of a Family Carrying the p.Asp1135Val Variant.

Researchers studied a family where both a child and father had autism and speech delays caused by a change in the TRIP12 gene. Unlike other cases of this genetic condition, they didn't have the typical facial features or severe intellectual disability. This shows that genetic changes in TRIP12 can cause autism and speech problems on their own, without other obvious signs. This finding helps doctors know when to test for this gene change in children with autism and speech delays.

This case report describes a family with a missense variant (p.Asp1135Val) in the TRIP12 gene, associated with Clark-Baraitser syndrome. Both the proband and father presented with autism spectrum disorder and speech delays without the typical facial features or severe intellectual disability often seen in this condition. The study reinforces that TRIP12 missense variants can cause milder neurodevelopmental presentations, with ASD and speech disorders occurring as isolated findings. This highlights the importance of genetic testing for TRIP12 variants in individuals with ASD and language disorders, even when classic syndromic features are absent, supporting improved genetic counseling and diagnosis.

Supports inclusion of TRIP12 gene analysis in genetic testing panels for ASD and speech disorders, even without classic syndromic features. Informs genetic counseling about variable phenotypic expression and potential for familial inheritance of milder TRIP12-related presentations.

Single family case report limits generalizability. No detailed developmental assessments or standardized autism diagnostic measures reported. Limited sample size prevents broader conclusions about TRIP12 variant penetrance and expressivity patterns.

Pathogenic variants in thegene are associated with Clark-Baraitser syndrome, a condition characterized by neurodevelopmental disorders, including intellectual disability, autism spectrum disorder (ASD), and speech delay. Phenotypic expression is variable, and facial features are not consistently present. Familial inheritance is rare. Whole-exome sequencing (WES) was performed on a proband with speech disorder and ASD, as well as on her parents.

Clinical assessment included developmental, cognitive, and physical evaluations. A heterozygous missense variant c.3404A>T (p. Asp1135Val) in thegene was identified in both the proband and her father. Both presented with speech disorder and ASD without facial features or severe intellectual disability.

In line with recent genotype-phenotype studies, missense TRIP12 variants tend to be associated with milder neurodevelopmental presentations, typically characterized by mild to moderate intellectual impairment, variable autistic traits, limited or absent facial features, and a low incidence of epilepsy. This familial case further presents the phenotypic spectrum ofmissense variants and highlights that ASD and speech disorder may occur as isolated neurodevelopmental findings without syndromic features. The report reinforces the relevance ofanalysis in the differential diagnosis of ASD and language disorders, even in individuals lacking physical traits, supporting more accurate genetic counseling and broader awareness of inherited TRIP12-related conditions.