Methylation Status in Medical Diagnosis and Treatment

Genetic Disorders Requiring Methylation Analysis

The American College of Medical Genetics recommends methylation analysis for Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) diagnosis, as it detects approximately 99% of cases 1
Methylation analysis using Southern hybridization with SNRPN or PW71B probes confirms PWS or AS diagnosis when only maternal or paternal alleles are present 1
If biparental inheritance is identified through methylation testing, both PWS and most identifiable causes of AS are ruled out 1
The American Academy of Pediatrics recommends methylation testing for individuals with intellectual disability, autism, learning disabilities, or family history of Fragile X syndrome 6

The National Comprehensive Cancer Network recommends determining MGMT promoter methylation status in glioblastoma, particularly in elderly or frail patients, to guide temozolomide treatment decisions 2
MGMT promoter methylation status is the single most important prognostic factor in the era of alkylating agent-based chemotherapy for gliomas 2
The American Society of Clinical Oncology recommends molecular methods, rather than immunocytochemistry, for determining MGMT promoter methylation status 2

The American College of Obstetricians and Gynecologists recommends methylation analysis as the appropriate diagnostic test for imprinted genetic disorders detected by noninvasive prenatal screening (NIPS) 10
When cytogenetic deletion is suspected on CVS or amniocentesis, the American College of Medical Genetics recommends performing FISH confirmation followed by methylation analysis if indicated 1

The College of American Pathologists recommends that methylation testing be performed at academic tertiary centers with specialized expertise and proper quality control measures 9
The National Institute of Standards and Technology recommends standardized assays with high interlaboratory agreement for MGMT promoter methylation testing 2