Population prevalence of copy number variants (CNVs)a first glimpse

Estimates of the population prevalence and inheritance patterns of recurrent copy number variants (CNVs) associated with neurodevelopmental disorders are lacking. This article presents a first glimpse.

It is well known that chromosome microdeletions or microduplications in several areas (1q21.1, 3q29, 15q11, 15q13, 16p11.2, etc) are associated with a wide range of neurodevelopmental disorders. At the same time in many cases the same microdeletions or microduplications can be found in the healthy parents of affected kids. However, the prevalence of such copy number variants (CNVs) in a general population remains unknown.

The authors studied the prevalence of several CNVs potentially causing neurodevelopmental disorders in a large cohort of unselected Norwegian families (mother-father-child). Participation in the study was offered to all pregnant women at 17 weeks of pregnancy, 41% agreed to participate. Families of non-Norwegian descent were excluded.

A total analysis of 12,252 families examined showed CNV s in 59 newborns. So basically 1 out of every 200 newborns in Norway has one such CNV. Approximately 2/3 of these CNVs (39/59) were inherited, ~1/3 occurred de novo. Out of 59 CNVs found in newborns 25 were deletions and 34 were duplications. The percentage of inherited cases was higher in patients with duplications compared to kids with deletions. There were 13 de novo deletions and only 7 de novo duplications.

Mothers and fathers of infants had CNVs with the same frequency (43 found in mothers and 44 in fathers). However, most inherited CNVs were of maternal origin (most likely there is a selection against sperm cells with CNVs).

Deletions 1q21.1 and proximal deletions 16p11.2 were found in 6 cases, each (~1:2000), deletions 15q13.3 in 5 (1:2500), duplications 15q11.2 and deletions 17q12 in 3 (~1:4000).

Although this data is preliminary it is the first glimpse of population prevalence of copy number variants.

Smajlagić D. et al. Population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders in 12,252 newborns and their parents. “Eur. J. Hum. Genet.” 2020 (ahead of print).

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