Frontiers in Genetics May 2017 – 22q11.2 deletion syndrome has a wide variety of symptoms, including (but not limited to) congenital heart disease, hypocalcemia (where the blood has too little calcium), immunological disorders, and psychiatric disorders. Palatal, craniofacial, skeletal, and gastroenterological anomalies are also common symptoms. Along with the range of symptoms, the severity differs from patient to patient.
To discover some of the reasons for this great variability in symptoms the authors analyzed two genetic features: a) exact position of the breakpoints, and b) structure of copy number variants (CNV) associated with deletions 22q11.2.
The study group consisted of 21 individuals - 9 males and 12 females - with a known 22q11.2 deletion, ranging in age from 3 months to 37 years. Of the 21 individuals tested, 18 had large, similar deletions in the 22q11.2 region (around 3 Mb in size). In these 18 individuals, this “common” deletion occurs withincertain breakpoints in the chromosome (specifically, between regions labeled LCR22-A and LCR22-D). The genes within these breakpoints do not contribute to the clinical signs of 22q11.2 deletion and, therefore, position of the breakpoints is not a potential reason for the variability in symptoms between individuals.
CNVs can influence the expression of the genes they inhabit, which can interact with other genes in the genome. The 3 Mb region contains about 50 genes, but the functions of all of these genes has not been fully explored. A large number of the genes in this region, are related to mitochondrial functions and non-coding RNAs (which include microRNAs). Mitochondria are necessary for providing energy to cells during development; therefore, some of the symptoms above may occur if the individual does not develop properly before birth. In persons with del 22q11.2 the authors found unusually high number of CNV affecting virtually all chromosomes, and almost all affected individuals had CNV which include microRNA genes. However, the authors did not provide information about spectrum and distribution of CNV in the control group of persons.
In summary, this study aimed to find the reason behind the variability in the severity of the symptoms of the 22q11.2 deletion by exploring the genes in the breakpoints of the deletion, and the common CNVs shared by individuals with the deletion. The evidence from the study shows that the genes within the breakpoints do not contribute to the variability. The CNVs, however, with their connection to microRNA production, may contribute. More research is necessary to determine if these genes within the CNVs directly relate to the symptoms of the deletions.