Duplication of 1q31.3q41 in two affected siblings due to paternal insertional translocation

We report two sisters with developmental delay and dysmorphic features, as well as a history of seizures. Both sisters have short stature, microcephaly and shared facial dysmorphisms. We detected an 18.1 Mb interstitial gain in 1q31.3q41 and a 140 kb interstitial loss in 7p11.2 in both siblings by using array analysis in the older sister and copy number variation analysis in whole exome sequencing data in the younger sister. We further examined parental chromosomes and found an insertional translocation in the unaffected father, having a 46,XY,ins(7;1)(p11.2;q31.3q41) karyotype. A 1.8 Mb loss at the rearranged 1q segment was subsequently detected on additional array analysis in the father, as well as the 140 kb loss in 7p11.2. We describe the clinical consequences of the 18.1 Mb duplication of the long arm of chromosome 1 due to an unbalanced paternal insertional translocation and compare these with the clinical phenotypes of patients with an overlapping 1q duplication.