Autism risk in offspring can be assessed through quantification of male sperm mosaicism.

Abstract:

:De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.

journal_name

Nat Med

journal_title

Nature medicine

authors

Breuss MW,Antaki D,George RD,Kleiber M,James KN,Ball LL,Hong O,Mitra I,Yang X,Wirth SA,Gu J,Garcia CAB,Gujral M,Brandler WM,Musaev D,Nguyen A,McEvoy-Venneri J,Knox R,Sticca E,Botello MCC,Uribe Fenner J,Pérez MC

doi

10.1038/s41591-019-0711-0

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

143-150

issue

1

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-019-0711-0

journal_volume

26

pub_type

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