SHANK3 Haploinsufficiency: a "common" but Underdiagnosed Highly Penetrant Monogenic Cause of Autism Spectrum Disorders

Overview

Journal Mol Autism

Publisher Biomed Central

Date 2013 Jun 14

PMID 23758743

Citations 120

Authors

Catalina Betancur

Joseph D Buxbaum

Affiliations

Soon will be listed here.

Abstract

Autism spectrum disorders (ASD) are etiologically heterogeneous, with hundreds of rare, highly penetrant mutations and genomic imbalances involved, each contributing to a very small fraction of cases. In this issue of Molecular Autism, Soorya and colleagues evaluated 32 patients with Phelan-McDermid syndrome, caused by either deletion of 22q13.33 or SHANK3 mutations, using gold-standard diagnostic assessments and showed that 84% met criteria for ASD, including 75% meeting criteria for autism. This study and prior studies demonstrate that this syndrome appears to be one of the more penetrant causes of ASD. In this companion review, we show that in samples ascertained for ASD, SHANK3 haploinsufficiency is one of the more prevalent monogenic causes of ASD, explaining at least 0.5% of cases. We note that SHANK3 haploinsufficiency remains underdiagnosed in ASD and developmental delay, although with the increasingly widespread use of chromosomal microarray analysis and targeted sequencing of SHANK3, the number of cases is bound to rise.

Citing Articles

Behavioral decline in Shank3 mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes.

Kshetri R, Beavers J, Hyde R, Ewa R, Schwertman A, Porcayo S Mol Autism. 2024; 15(1):52.

PMID: 39633421 PMC: 11616285. DOI: 10.1186/s13229-024-00628-y.

Metataxonomic and Immunological Analysis of Feces from Children with or without Phelan-McDermid Syndrome.

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Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome.

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PMID: 39363263 PMC: 11451156. DOI: 10.1186/s11689-024-09572-7.

Behavioral regression in shank3 mice during early adulthood corresponds to cerebellar granule cell glutamatergic synaptic changes.

Kshetri R, Beavers J, Hyde R, Ewa R, Schwertman A, Porcayo S Res Sq. 2024; .

PMID: 39281868 PMC: 11398578. DOI: 10.21203/rs.3.rs-4888950/v1.

Genetic Mutations Associated With TNFAIP3 (A20) Haploinsufficiency and Their Impact on Inflammatory Diseases.

Bagyinszky E, An S Int J Mol Sci. 2024; 25(15).

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