Abstract
Chromosome 15 imprinting disorders include Prader-Willi (PWS) and Angelman (AS) syndromes, which are caused by absent expression from the paternal and maternal alleles in the chromosome 15q11. 2–q13 region, respectively. In addition, chromosome 15q duplication caused by the presence of at least one additional maternally derived copy of the 15q11.2–q13 region can lead to seizures, cognitive and behavioral problems. We focus on PWS and AS in the report, and expand the discussion of clinical care and description with genetic testing to include high-resolution studies to more specifically characterize the molecular mechanisms of disease. The importance of early diagnosis with the necessity for accurate molecular characterization through a step-wise algorithm is emphasized in an era of targeted therapeutic interventions. We present a flowchart to aid in ordering specialized genetic testing as several methods are available for patients presenting with features of PWS and/or AS.
Highlights
The chromosome 15 imprinting disorders include Prader-Willi (PWS) and Angelman (AS) syndromes [1,2,3,4,5,6] and chromosome 15q duplications
We focused on Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in this report as both syndromes are detected via DNA methylation testing, which allows for determination of the active parental gene allele and definitive diagnosis in individuals with PWS and in most individuals with AS [2]
There are three recognized PWS molecular classes including a paternal 15q11–q13 deletion about 5–6 Mb in size (60% of cases) and maternal disomy 15 (UPD15) in which both chromosome 15s are inherited from the mother (36%) originating from trisomy 15 with loss of the paternal chromosome 15 in early pregnancy leading to two chromosome 15s from the mother [16]
Summary
The chromosome 15 imprinting disorders include Prader-Willi (PWS) and Angelman (AS) syndromes [1,2,3,4,5,6] and chromosome 15q duplications. For AS, DNA methylation testing identifies ∼80% of individuals, but again does not distinguish between the molecular classes or detect a mutation in the UBE3A gene causing AS.
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