Microduplication and triplication of 22q11.2: a highly variable syndrome

Area of Science:

• Genetics
• Human Genetics
• Molecular Biology

Background:

• 22q11.2 microdeletions are common, but microduplications of the same region are rarely reported.
• Theoretically, 22q11.2 microduplications should occur with similar frequency to deletions.
• The clinical presentation of 22q11.2 microduplications is poorly understood and highly variable.

Purpose of the Study:

• To investigate the frequency and phenotypic spectrum of 22q11.2 microduplications.
• To evaluate different screening methods for identifying 22q11.2 microduplications.
• To report the first case of 22q11.2 triplication and familial microduplication.

Main Methods:

• Screening of 275 females negative for Fragile X syndrome using four different methods.
• Real-time polymerase chain reaction (PCR) for efficient detection of microduplications.
• Karyotyping and chromosomal analysis for identifying triplications and familial abnormalities.

Main Results:

• Two previously unreported 22q11.2 microduplications were identified in the Fragile X-negative cohort.
• The ascertainment rate in the Fragile X-negative cohort was double that of the cohort screened for 22q11.2 deletion.
• The first patient with 22q11.2 triplication was reported, with the mother carrying a microduplication.
• Several phenotypically normal parents were found to be carriers of 22q11.2 microduplications.

Conclusions:

• 22q11.2 microduplications present with a wide range of phenotypes, complicating diagnosis.
• Real-time PCR is an effective screening tool for identifying 22q11.2 microduplications.
• Family members of affected individuals should be tested for 22q11.2 microduplications due to potential asymptomatic carrier status.