Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects

Beate Peter, Valentin Dinu, Li Liu, Matthew Huentelman, Marcus Naymik, Hope Lancaster, Caitlin Vose, Isabelle Schrauwen

Research output: Contribution to journalArticle

Abstract

Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.

Original languageEnglish (US)
JournalBehavior Genetics
DOIs
StatePublished - Jan 1 2019

Fingerprint

Exome
Siblings
Apraxias
childhood
gene
mutation
Genetic Pleiotropy
nuclear family
Mutation
genes
postnatal development
Nuclear Family
heterozygosity
Genes
Comorbidity
brain
Nucleotides
nucleotides
Autism Spectrum Disorder
Speech Sound Disorder

Keywords

  • Autism spectrum disorder
  • Childhood apraxia of speech
  • Comorbidity
  • Complex trait
  • Heterogeneity
  • Language impairment
  • Multiple hits

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

Cite this

Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects. / Peter, Beate; Dinu, Valentin; Liu, Li; Huentelman, Matthew; Naymik, Marcus; Lancaster, Hope; Vose, Caitlin; Schrauwen, Isabelle.

In: Behavior Genetics, 01.01.2019.

Research output: Contribution to journalArticle

@article{06d97ccd9abd48b39435f54a8a254afb,
title = "Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects",
abstract = "Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.",
keywords = "Autism spectrum disorder, Childhood apraxia of speech, Comorbidity, Complex trait, Heterogeneity, Language impairment, Multiple hits",
author = "Beate Peter and Valentin Dinu and Li Liu and Matthew Huentelman and Marcus Naymik and Hope Lancaster and Caitlin Vose and Isabelle Schrauwen",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s10519-019-09957-8",
language = "English (US)",
journal = "Behavior Genetics",
issn = "0001-8244",
publisher = "Springer New York",

}

TY - JOUR

T1 - Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects

AU - Peter, Beate

AU - Dinu, Valentin

AU - Liu, Li

AU - Huentelman, Matthew

AU - Naymik, Marcus

AU - Lancaster, Hope

AU - Vose, Caitlin

AU - Schrauwen, Isabelle

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.

AB - Recent studies of autism spectrum disorder (ASD) and childhood apraxia of speech (CAS) have resulted in conflicting conclusions regarding the comorbidity of these disorders on phenotypic grounds. In a nuclear family with two dually affected and one unaffected offspring, whole-exome sequences were evaluated for single nucleotide and indel variants and CNVs. The affected siblings but not the unaffected sibling share a rare deleterious compound heterozygous mutation in WWOX, implicated both in ASD and motor control. In addition, one of the affected children carries a rare deleterious de novo mutation in the ASD candidate gene RIMS1. The two affected children but not their unaffected sibling inherited deleterious variants with relevance for ASD and/or CAS. WWOX, RIMS1, and several of the genes harboring the inherited variants are expressed in the brain during prenatal and early postnatal development. Results suggest compound heterozygosity as a cause of ASD and CAS, pleiotropic gene effects, and potentially additional, complex genetic effects.

KW - Autism spectrum disorder

KW - Childhood apraxia of speech

KW - Comorbidity

KW - Complex trait

KW - Heterogeneity

KW - Language impairment

KW - Multiple hits

UR - http://www.scopus.com/inward/record.url?scp=85064342874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064342874&partnerID=8YFLogxK

U2 - 10.1007/s10519-019-09957-8

DO - 10.1007/s10519-019-09957-8

M3 - Article

JO - Behavior Genetics

JF - Behavior Genetics

SN - 0001-8244

ER -