Revealing parental mosaicism: the hidden answer to the recurrence of apparent de novo variants

Human Genomics

Research

Raymond H. W. Li¹  Anita S. Y. Kan²  Joshua C. K. Chan³  Christopher C. Y. Mak³  Mianne Lee³  Adrian C. Y. Lui³  Anna K. Y. Kwong³  Phoenix H. L. Doong³  Brian H. Y. Chung⁴ 

[1] Department of Obstetrics and Gynaecology, Queen Mary Hospital, Pok Fu Lam, Hong Kong SAR, China;Department of Obstetrics and Gynaecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China;Department of Obstetrics and Gynaecology, Queen Mary Hospital, Pok Fu Lam, Hong Kong SAR, China;Department of Obstetrics and Gynaecology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China;Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital, Sai Wan Ho, Hong Kong SAR, China;Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Room 115, 1/F, New Clinical Building, Pok Fu Lam, Hong Kong SAR, China;Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, Room 115, 1/F, New Clinical Building, Pok Fu Lam, Hong Kong SAR, China;Department of Paediatrics and Adolescent Medicine, Hong Kong Children’s Hospital, Ngau Tau Kok, Hong Kong SAR, China;

关键词: Parental mosaicism;    Gonadal mosaicism;    Gonosomal mosaicism;    De novo mutation;    Recurrence risk;    Droplet digital PCR;   

DOI  :  10.1186/s40246-023-00535-y

 received in 2023-02-02, accepted in 2023-09-18,  发布年份 2023

来源: Springer

【 摘 要 】

Mosaicism refers to the presence of two or more populations of genetically distinct cells within an individual, all of which originate from a single zygote. Previous literature estimated the percentage of parental mosaicism ranged from 0.33 to 25.9%. In this study, parents whose children had previously been diagnosed with developmental disorders with an apparent de novo variant were recruited. Peripheral blood, buccal and semen samples were collected from these parents if available for the detection of potential parental mosaicism using droplet digital PCR, complemented with the method of blocker displacement amplification. Among the 20 families being analyzed, we report four families with parental mosaicism (4/20, 20%). Two families have maternal gonosomal mosaicism (EYA1 and EBF3) and one family has paternal gonadal mosaicism (CHD7) with a pathogenic/ likely pathogenic variant. One family has a paternal gonosomal mosaicism with a variant of uncertain significance (FLNC) with high clinical relevance. The detectable variant allele frequency in our cohort ranged from 8.7–35.9%, limit of detection 0.08–0.16% based on our in-house EBF3 assay. Detecting parental mosaicism not only informs family with a more accurate recurrence risk, but also facilitates medical teams to create appropriate plans for pregnancy and delivery, offering the most suitable care.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 6

Fig. 4

Fig. 3

Fig. 2

Fig. 1