Autism

Gene: TNRC6B

Green List (high evidence)

17 unrelated individuals with heterozygous TNRC6B variants reported. Features included hypotonia (10/17), DD/ID (17/17 - ID was not universal: average IQ of 12 individuals was 73 (range : 50-113) with 4 having below 70), ADHD (11/17), ASD or autistic traits (8/17 and 5/17). Some/few presented with abnormal OFC (micro- / macrocephaly in 3/17 and 2/17), abnormal vision or hearing, variable other congenital anomalies, echocardiographic, GI or renal abnormalities, etc. Epilepsy was reported in 1/17. There was no recognisable gestalt.Detected variants included 14 pLoF, 1 missense SNV and 2 intragenic deletions. Variants had occurred as de novo events in 10/13 subjects for whom testing of both parents was possible. 3/13 subjects had inherited the variant from a parent with milder phenotype. Based on the type of variants identified, the pLI score of 1 in gnomAD and the HI index of 5.61%, the authors suggest haploinsufficiency as the most likely mechanism. Individuals with de novo TNRC6B variants have also been reported in larger cohorts (e.g. DDD study - PMID: 28135719, Iossifov et al - PMID: 25363768, Lelieveld et al - PMID: 27479843, Jónsson et al - PMID: 28959963). A previous study provided details on 2 sibs harboring a translocation which disrupted both TNRC6B and TCF20 (also associated with ID)(Babbs et al - PMID: 25228304).

Created: 7 May 2020, 1:25 a.m. | Last Modified: 7 May 2020, 1:25 a.m.

Panel Version: 0.86

No evidence currently for Mendelian disease association.

Created: 20 Nov 2019, 7:29 p.m. | Last Modified: 20 Nov 2019, 7:29 p.m.

Panel Version: 0.13

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay with speech and behavioural abnormalities, MIM# 619243

Publications

• 32152250
• 28135719
• 25363768
• 27479843
• 28959963
• 25228304