Abstract
BackgroundWe present genomic and phenotypic findings of a transgenerational family consisting of three male offspring, each with a maternally inherited distal 220 kb deletion at locus 16p11.2 (BP2–BP3). Genomic analysis of all family members was prompted by a diagnosis of autism spectrum disorder (ASD) in the eldest child, who also presented with a low body mass index.MethodsAll male offspring underwent extensive neuropsychiatric evaluation. Both parents were also assessed for social functioning and cognition. The family underwent whole-genome sequencing. Further data curation was undertaken from samples ascertained for neurodevelopmental disorders and congenital abnormalities.ResultsOn medical examination, both the second and third-born male offspring presented with obesity. The second-born male offspring met research diagnostic criteria for ASD at 8 years of age and presented with mild attention deficits. The third-born male offspring was only noted as having motor deficits and received a diagnosis of developmental coordination disorder. Other than the 16p11.2 distal deletion, no additional contributing variants of clinical significance were observed. The mother was clinically evaluated and noted as having a broader autism phenotype.ConclusionIn this family, the phenotypes observed are most likely caused by the 16p11.2 distal deletion. The lack of other overt pathogenic mutations identified by genomic sequencing reinforces the variable expressivity that should be heeded in a clinical setting. Importantly, distal 16p11.2 deletions can present with a highly variable phenotype even within a single family. Our additional data curation provides further evidence on the variable clinical presentation among those with pathogenetic 16p11.2 (BP2–BP3) mutations.
Funder
The Hospital for Sick Children
The Centre for Applied Genomics
Autism Speaks
Canada Foundation for Innovation (CFI), Government of Ontario, Canadian Institutes of Health Research (CIHR), SickKids
Ontario Brain Institute
University of Toronto McLaughlin Centre
University of Toronto
SickKids
SAGE
NIH
Environment and Health Initiative
Geneva Coordinating Center
National Center for Biotechnology Information
Johns Hopkins University Center for Inherited Disease Research
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse
Smoking Cessation
Center for Inherited Disease Research
National Institutes of Health
Coordinating Center
University of Wisconsin Transdisciplinary Tobacco Use Research Center
The NEI Refractive Error Collaboration
National Eye Institute
NEIREC
NEIREC Research Group
Subject
Genetics (clinical),Genetics
Cited by
1 articles.
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