Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Microduplication 22q11.2 [Q92]

OMIM number: 608363

Dr. med. Imma Rost

Scientific Background

While the microdeletion 22q11.2 occurs with a frequency of up to 1:4,000, microduplications of the same region only occur half as much, although due to their underlying mechanism (NAHR: non-allelic homologous recombination occurring between low-copy repeats), the same frequency could be expected. This may partially be due to the very variable or mild phenotype, which rarely gives rise to diagnostic procedures. Furthermore, a duplication is harder to find in the commonly used FISH analysis of metaphases (two signals located closely to each other) than a deletion (missing signal). To detect duplications, FISH analysis on interphase nuclei is more suitable. Possible alternatives are MLPA as well as array CGH. Most patients exhibit an approx. 3 Mb large duplication, which is frequently already present in one of the parents.

The signs and symptoms vary strongly also within the family, partially overlapping with the microdeletion 22q11.2, and may range from cardiac and urogenital malformations, velopharyngeal insufficiency, minor learning difficulties to asymptomatic carriers of a duplication. Physical features include superior placement of eyebrows, wide-set eyes with downslanting palpebral fissures, mild micro/retrognathia and minor ear anomalies. Hearing impairment occurs in almost half of all patients. The duplicated region contains the TBX1 gene. Its loss is considered to cause most signs and symptoms regarding the microdeletion. The mouse modell showed that also the over expression of this gene, as to be expected in the case of a duplication, causes similar signs and symptoms as the haploinsufficiency. This may be an explanation for the overlapping of the signs and symptoms of the microdeletion and microduplication 22q11.2.