Abnormalities of the DNA Methylation Mark and Its Machinery
Abnormalities of the DNA Methylation Mark and Its Machinery
When a disorder of methylation or imprinting is suspected, there are several clinically available molecular methods which clinicians can use to assist in making the diagnosis. When suspicion of a single gene disorder of the DNA methylation machinery such as Rett syndrome is high, specific sequencing of that gene with or without deletion and duplication testing of that gene can be performed clinically. Deletions or duplications of larger chromosomal regions can be assessed through high-resolution chromosomal microarrays, and this can also reveal some cases of uniparental disomy (isodisomy). When an imprinting disorder is suspected, methylation testing of the relevant area is warranted. If methylation tests are abnormal, a diagnosis of an imprinting disorder is made. If multiple methylation tests of a locus are abnormal, segregation of DNA polymorphisms can be analyzed to investigate for uniparental disomy (heterodisomy). Imprinting control regions can also be sequenced. For MLMD, multiple methylation assays can be sent, although in the future it may be possible to explore this on a more global scale.
Diagnostic Workup for Imprinting Disorders and MDMM
When a disorder of methylation or imprinting is suspected, there are several clinically available molecular methods which clinicians can use to assist in making the diagnosis. When suspicion of a single gene disorder of the DNA methylation machinery such as Rett syndrome is high, specific sequencing of that gene with or without deletion and duplication testing of that gene can be performed clinically. Deletions or duplications of larger chromosomal regions can be assessed through high-resolution chromosomal microarrays, and this can also reveal some cases of uniparental disomy (isodisomy). When an imprinting disorder is suspected, methylation testing of the relevant area is warranted. If methylation tests are abnormal, a diagnosis of an imprinting disorder is made. If multiple methylation tests of a locus are abnormal, segregation of DNA polymorphisms can be analyzed to investigate for uniparental disomy (heterodisomy). Imprinting control regions can also be sequenced. For MLMD, multiple methylation assays can be sent, although in the future it may be possible to explore this on a more global scale.
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