Biomedical subjects

Theresia Herget

Publications and source records attributed to Theresia Herget.

3 recordsLinked to original sources

PubMed2025

AUTS2-related syndrome: Insights from a large European cohort.

PURPOSE: AUTS2-related syndrome is characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters, AUTS2 encodes 2 distinct long and short isoforms encoding a putative transcriptional activator. METHODS: Through a European collaborative study, we collected clinical and genotype data on the largest AUTS2-related syndrome cohort of 58 patients harboring genomic rearrangements or single-nucleotide variants (SNVs). RESULTS: Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent of the underlying defect at the AUTS2 locus, we observed that autistic behavior, hyperactivity, learning difficulties, and speech delay are common features of AUTS2-related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both longer and shorter AUTS2 transcripts showed a recognizable phenotype with microcephaly, brachycephaly, microretrognathia, broad nasal base, and anteverted nares. Behavioral disorders were more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only observed in patients with SNVs. CONCLUSION: This study provides a comprehensive clinical characterization of AUTS2-related syndrome, reveals few genotype-phenotype correlations, and suggests that the disruption of the 2 distinct AUTS2 transcripts has a different impact on the clinical phenotype.

Humans↗

PubMed2024

Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.

PURPOSE: The thousand and one kinase (TAOK) proteins are a group of serine/threonine-protein kinases involved in signaling pathways, cytoskeleton regulation, and neuronal development. TAOK1 variants are associated with a neurodevelopmental disorder (NDD) characterized by distinctive facial features, hypotonia, and feeding difficulties. TAOK2 variants have been reported to be associated with autism and early-onset obesity. However, a distinct TAOK2-NDD has not yet been delineated. METHODS: We retrospectively studied the clinical and genetic data of individuals recruited from several centers with TAOK1 and TAOK2 variants that were detected through exome and genome sequencing. RESULTS: We report 50 individuals with TAOK1 variants with associated phenotypes, including neurodevelopmental abnormalities (100%), macrocephaly (83%), and hypotonia (58%). We report male genital anomalies and hypoglycemia as novel phenotypes. Thirty-seven unique TAOK1 variants were identified. Most of the missense variants clustered in the protein kinase domain at residues that are intolerant to missense variation. We report 10 individuals with TAOK2 variants with associated phenotypes, including neurodevelopmental abnormalities (100%), macrocephaly (75%), autism (75%), and obesity (70%). CONCLUSION: We describe the largest cohort of TAOK1-NDD to date, to our knowledge, expanding its phenotype and genotype spectrum with 30 novel variants. We delineated the phenotype of a novel TAOK2-NDD associated with neurodevelopmental abnormalities, autism, macrocephaly, and obesity.

Humans↗

PubMed2022

Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.

Humans↗