22q11.2 duplication, bladder exstrophy and the LZTR1 gene

chromosome 22

22q11.2 duplication, bladder exstrophy and the LZTR1 gene

Bladder exstrophy is a rare birth defect resulting in the malformation of the bladder and urethra. It is part of the bladder exstrophy-epispadias complex (BEEC). In several previously published reports children with bladder exstrophy were found to have duplications of the 22q11.2 area (although the vast majority of patients with dup 22q11.2 do not have this defect).

The authors performed array comparative genomic hybridization (array-CGH) of 76 Swedish patients with BEEC and found three patients with 22q11.2 microduplications, including inherited and de novo microduplications (occurring spontaneously and not inherited from parents). The increase of duplication 22q11.2 among patients with BEEC is highly significant statistically.

The authors also analyzed the protein coding genes in the 22q11.2 region of twenty BEEC patients without 22q11.2 duplications. One patient had a missense variant in the LZTR1 gene, predicted to be pathogenic. Previous studies in mouse models have also identified the LZTR1 gene as a potential gene that contributes to the BEEC phenotype. The authors concluded that the LZTR1 variant should be considered a prospective candidate gene in the genetic component of BEEC.

Lundin J, Markljung E, Baranowska Körberg I, et al. Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene. Mol Genet Genomic Med. 2019, v. 7 (6), e666.

Articles of the month are chosen from newly published genetic research by CDO geneticist, Dr. Iosif Lurie.  For more information on any article please contact info@chromodisorder.org