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 Medjournal_title
Nature medicineauthors
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 MCdoi
10.1038/s41591-019-0711-0subject
Has Abstractpub_date
2020-01-01 00:00:00pages
143-150issue
1eissn
1078-8956issn
1546-170Xpii
10.1038/s41591-019-0711-0journal_volume
26pub_type
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