Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience
22q11.2 region is rich in low copy repeats (large repetitive blocks of DNA that are similar to each other), which makes the region prone to both deletions and duplications during meiosis. Deletions of 22q11.2 are very common. Microduplications of this region are reported less frequently.
Patients with 22q11.2 duplication reveal a range of highly variable clinical features that include facial dysmorphisms, cardiac abnormalities, neurological deficiencies, muscular hypotonia, and respiratory insufficiencies. Prior studies have also found 22q11.2 duplication patients that were either diagnosed with autism spectrum disorder (ASD) or exhibited features of ASD. The article reports on nine patients with 22q11.2 duplication in order to examine region specific genotype–phenotype associations.
Four of the patients in the study shared similar proximal 22q11.2 duplications. Shared clinical features of these four patients included congenital cardiovascular defects in patients 2-4 and psychomotor delays among patients 1-3. However, the risk for these clinical features is hard to determine, as the authors found that the estimated penetrance was 22%.
Duplications in patients 7, 8, 9 were distal duplications that have been associated with reduced penetrance and uncertain pathogenicity in prior studies. Patients 8 and 9, being healthy adults, further supported these findings. The authors recommend that further investigations research the pathogenicity of these distal duplications.
The authors conclude that the genotype–phenotype associations among 22q11.2 duplication patients are associated with unpredictability.
Yu, A. et al. “Genotypic and phenotypic variability of 22q11.2 microduplications: an institutional experience.” American Journal of Medical Genetics Part A, 2019, vol. 179, pp. 2178–2189.
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