Both 17q12 duplication and deletion detected in the patient with normal phenotype and their segregation in family with variably affected members
Abstract
Chromosomal band 17q12 is a gene rich region flanked by segmental duplications which make the region prone to deletions and duplication by NAHR mechanism (non-allelic homologous recombination). While the deletions cause well described clinical unit with specific phenotype called RCAD (renal cyst and diabetes mellitus), the phenotype caused by reciprocal duplications of the same region still remains unclear especially due to variable expressivity and incomplete penetrance and fact, that they are often detected in healthy patients.
Here we present unusual case of family where the mother is carrier of duplication (paternally inherited) and also deletion (from mother with RCAD) of the identical 17q12 region. All of her children were diagnosed with 17q12 microduplication syndrome.
Except of the mother and grandfather, all her children carrying duplication express variable degree of neurodevelopmental problems, such as epilepsy, mild intellectual disability, delayed speech development or attention deficit disorder, that correlate with the hypothesis of incomplete penetrance and variable phenotype published by many studies. As a potential causative genes are considered LHX1 for neurodevelopmental problems and gene ACACA for epilepsy.
The simultaneous occurrence of deletion and duplication of the same chromosomal region in one family is very rare. This case supports hypothesis that 17q12 duplications are stable and may segregate in a family for several generations.
Supported by: 00064203, NF-CZ11-PDP-3-003-2014, AZV17-29423A