Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype

Krysta J Trevis; Natasha J Brown; Cherie C Green; Paul J Lockhart; Tarishi Desai; Tanya Vick; Vicki Anderson; Emmanuel P K Pua; Melanie Bahlo; Martin B Delatycki; Ingrid E Scheffer; Sarah J Wilson

doi:10.3390/ijms21217965

Tracing Autism Traits in Large Multiplex Families to Identify Endophenotypes of the Broader Autism Phenotype

Int J Mol Sci. 2020 Oct 27;21(21):7965. doi: 10.3390/ijms21217965.

Authors

Krysta J Trevis^{1

2}, Natasha J Brown^{3

4}, Cherie C Green^{1

2

5}, Paul J Lockhart^{6

7}, Tarishi Desai^{1

2}, Tanya Vick⁴, Vicki Anderson^{2

8

9}, Emmanuel P K Pua¹, Melanie Bahlo^{10

11}, Martin B Delatycki^{3

6

7}, Ingrid E Scheffer^{1

3

9

12}, Sarah J Wilson^{1

2

12}

Affiliations

¹ Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC 3084, Australia.
² Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
³ Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁴ Barwon Health, Geelong, VIC 3220, Australia.
⁵ Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Bundoora, VIC 3086, Australia.
⁶ Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁷ Department of Paediatrics, The University of Melbourne, Parkville, VIC 3010, Australia.
⁸ Psychological Service, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
⁹ Clinical Sciences Research, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
¹⁰ Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
¹¹ Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
¹² The Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3052, Australia.

Abstract

Families comprising many individuals with Autism Spectrum Disorders (ASD) may carry a dominant predisposing mutation. We implemented rigorous phenotyping of the "Broader Autism Phenotype" (BAP) in large multiplex ASD families using a novel endophenotype approach for the identification and characterisation of distinct BAP endophenotypes. We evaluated ASD/BAP features using standardised tests and a semi-structured interview to assess social, intellectual, executive and adaptive functioning in 110 individuals, including two large multiplex families (Family A: 30; Family B: 35) and an independent sample of small families (n = 45). Our protocol identified four distinct psychological endophenotypes of the BAP that were evident across these independent samples, and showed high sensitivity (97%) and specificity (82%) for individuals classified with the BAP. Patterns of inheritance of identified endophenotypes varied between the two large multiplex families, supporting their utility for identifying genes in ASD.

Keywords: Broader Autism Phenotype; autism spectrum disorder; genetic; multiplex family.

MeSH terms

Adolescent
Adult
Aged
Autism Spectrum Disorder / diagnosis*
Autism Spectrum Disorder / psychology
Child
Child, Preschool
Early Diagnosis
Endophenotypes / analysis*
Family / psychology*
Female
Humans
Male
Middle Aged
Pedigree
Young Adult

Abstract

MeSH terms

Grants and funding