Groups 1 to 3 | Copy number not variable in the normal population. Chromosomal segments of several megabases in size; copy number change usually plus or minus one. Most have phenotypic consequences. | Copy number variable in the normal population. Pseudogene or gene casettes of limited extent; relatively high copy number changes needed for cytogenetic visibility. None has established phenotypic consequences. |
Group 1: normal offspring with normal parents | n = 23 (18%). Most group 1 families ascertained at prenatal diagnosis. Unknown whether post-natally ascertained cases would also be free of phenotypic effect. Homozygous imbalances of the same type unlikely to be equally free of phenotypic consequences. | n = 38 (54%). Most group 1 families ascertained at prenatal diagnosis. Assumed that postnatally ascertained cases also free of phenotypic effect. Homozygous copy number variants unlikely to have significant phenotypic consequences. |
Group 2: affected offspring with normal parents | n = 30 (23%). Most group 2 families ascertained via phenotype of offspring. Some likely to be coincidental to phenotype, some causal and some of uncertain significance. | n = 30 (43%). Most group 2 families ascertained via phenotype of offspring. Phenotype of probands assumed to reflect ascertainment bias in all cases. |
Group 3: affected offspring with affected parents | n = 77 (59%). Common co-segregation of group 3 imbalance and mild phenotype common and likely to be causal in the great majority of families. | n = 2 (3%). Rare co-segregation of group 3 variant and mild phenotype regarded as coincidental in both families. |