Characterization of Intellectual Disability and Autism Comorbidity Through Gene Panel Sequencing

Overview

Journal Hum Mutat

Specialty Genetics

Date 2019 Jun 19

PMID 31209962

Citations 28

Authors

Maria C Aspromonte

Mariagrazia Bellini

Alessandra Gasparini

Marco Carraro

Elisa Bettella

Roberta Polli

Federica Cesca

Stefania Bigoni

Stefania Boni

Ombretta Carlet

Susanna Negrin

Isabella Mammi

Donatella Milani

Angela Peron

Stefano Sartori

Irene Toldo

Fiorenza Soli

Licia Turolla

Franco Stanzial

Francesco Benedicenti

Cristina Marino-Buslje

Silvio C E Tosatto

Alessandra Murgia

Emanuela Leonardi

Affiliations

Soon will be listed here.

Abstract

Intellectual disability (ID) and autism spectrum disorder (ASD) are clinically and genetically heterogeneous diseases. Recent whole exome sequencing studies indicated that genes associated with different neurological diseases are shared across disorders and converge on common functional pathways. Using the Ion Torrent platform, we developed a low-cost next-generation sequencing gene panel that has been transferred into clinical practice, replacing single disease-gene analyses for the early diagnosis of individuals with ID/ASD. The gene panel was designed using an innovative in silico approach based on disease networks and mining data from public resources to score disease-gene associations. We analyzed 150 unrelated individuals with ID and/or ASD and a confident diagnosis has been reached in 26 cases (17%). Likely pathogenic mutations have been identified in another 15 patients, reaching a total diagnostic yield of 27%. Our data also support the pathogenic role of genes recently proposed to be involved in ASD. Although many of the identified variants need further investigation to be considered disease-causing, our results indicate the efficiency of the targeted gene panel on the identification of novel and rare variants in patients with ID and ASD.

Citing Articles

Genetic variants and phenotypic data curated for the CAGI6 intellectual disability panel challenge.

Aspromonte M, Del Conte A, Polli R, Baldo D, Benedicenti F, Bettella E Hum Genet. 2025; .

PMID: 40019509 DOI: 10.1007/s00439-025-02733-1.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

Aspromonte M, Del Conte A, Zhu S, Tan W, Shen Y, Zhang Y Hum Genet. 2025; .

PMID: 39786577 DOI: 10.1007/s00439-024-02722-w.

Broadening the scope of multigene panel analysis for adult epilepsy patients.

Lee S, Kang M, So K, Jang R, Shin Y, Jang S Epilepsia Open. 2024; 9(4):1538-1549.

PMID: 38946282 PMC: 11296137. DOI: 10.1002/epi4.12993.

Genetic Diagnosis in Children with Developmental Delay.

Hung K Children (Basel). 2024; 11(6).

PMID: 38929248 PMC: 11201514. DOI: 10.3390/children11060669.

CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods.

Genome Biol. 2024; 25(1):53.

PMID: 38389099 PMC: 10882881. DOI: 10.1186/s13059-023-03113-6.

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