Journal article
The utility of cerebrospinal fluid-derived cell-free DNA in molecular diagnostics for the PIK3CA -related megalencephaly-capillary malformation (MCAP) syndrome: a case report
Cold Spring Harbor molecular case studies, Vol.8(3), p.1
04/2022
DOI: 10.1101/mcs.a006188
PMCID: PMC9059787
PMID: 35483878
Abstract
The megalencephaly-capillary malformation (MCAP) syndrome is an overgrowth disorder caused by mosaic gain-of-function variants in
It is characterized by megalencephaly or hemimegalencephaly, vascular malformations, somatic overgrowth, among other features. Epilepsy is commonly associated with MCAP, and a subset of individuals have cortical malformations requiring resective epilepsy surgery. Like other mosaic disorders, establishing a molecular diagnosis is largely achieved by screening lesional tissues (such as brain or skin), with a low diagnostic yield from peripheral tissues (such as blood). Therefore, in individuals with MCAP in whom lesional tissues are scarce or unavailable or those ineligible for epilepsy surgery, establishing a molecular diagnosis can be challenging. Here we report on the utility of cerebrospinal fluid (CSF)-derived cfDNA for the molecular diagnosis of an individual with MCAP syndrome harboring a mosaic
variant (c.3139C > T, p.His1047Tyr). The proband presented with asymmetric megalencephaly without significant dysgyria. He did not have refractory epilepsy and was therefore not a candidate for epilepsy surgery. However, he developed diffuse large B-cell lymphoma (DLBCL) in late childhood, with four CSF samples obtained via lumbar puncture for cancer staging during which one sample was collected for cfDNA extraction and sequencing.
variant allele fractions in CSF cell-free DNA (cfDNA), skin fibroblasts, and peripheral blood were 3.08%, 37.31%, and 2.04%, respectively. This report illustrates the utility of CSF-derived cfDNA in MCAP syndrome. Minimally invasive-based molecular diagnostic approaches utilizing cfDNA not only facilitate accurate genetic diagnosis but also have important therapeutic implications for individuals with refractory epilepsy as repurposed PI3K-AKT-MTOR pathway-inhibitors become more widely available.
Details
- Title: Subtitle
- The utility of cerebrospinal fluid-derived cell-free DNA in molecular diagnostics for the PIK3CA -related megalencephaly-capillary malformation (MCAP) syndrome: a case report
- Creators
- Wei-Liang Chen - University of Washington Medical CenterEmily Pao - Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USAJames Owens - University of WashingtonIan Glass - University of WashingtonColin Pritchard - University of WashingtonBrain H Shirts - University of WashingtonChristina Lockwood - University of WashingtonGhayda M Mirzaa - University of Washington
- Resource Type
- Journal article
- Publication Details
- Cold Spring Harbor molecular case studies, Vol.8(3), p.1
- DOI
- 10.1101/mcs.a006188
- PMID
- 35483878
- PMCID
- PMC9059787
- ISSN
- 2373-2873
- eISSN
- 2373-2873
- Grant note
- T32 GM007454 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Stead Family Department of Pediatrics; Neurology (Pediatrics)
- Record Identifier
- 9984701645202771
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