Survival of a male patient harboring CASK Arg27Ter mutation to adolescence

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dc.contributor.authorMukherjee, Konarken
dc.contributor.authorPatel, Paras A.en
dc.contributor.authorRajan, Deepa S.en
dc.contributor.authorLaConte, Leslie E. W.en
dc.contributor.authorSrivastava, Sarikaen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-09-02T14:54:05Zen
dc.date.available2021-09-02T14:54:05Zen
dc.date.issued2020-07-21en
dc.date.updated2021-09-02T14:54:02Zen
dc.description.abstractBackground: CASK is an X-linked gene in mammals and its deletion in males is incompatible with life. CASK heterozygous mutations in female patients associate with intellectual disability, microcephaly, pontocerebellar hypoplasia, and optic nerve hypoplasia, whereas CASK hemizygous mutations in males manifest as early infantile epileptic encephalopathy with a grim prognosis. Here, we report a rare case of survival of a male patient harboring a CASK null mutation to adolescent age. Methods: Trio whole exome sequencing analysis was performed from blood genomic DNA. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electroencephalogram (EEG) analyses were performed to determine anomalies in brain development, metabolite concentrations, and electrical activity, respectively. Results: Trio-WES analysis identified a de novo c.79C>T (p.Arginine27Ter) mutation in CASK causing a premature translation termination at the very N-terminus of the protein. The 17-years, and 11-month-old male patient displayed profound intellectual disability, microcephaly, dysmorphism, ponto-cerebellar hypoplasia, and intractable epilepsy. His systemic symptoms included overall reduced somatic growth, dysautonomia, ventilator and G tube dependence, and severe osteopenia. Brain MRI revealed a severe cerebellar and brain stem hypoplasia with progressive cerebral atrophy. EEG spectral analysis revealed a global functional defect with generalized background slowing and delta waves dominating even in the awake state. Conclusion: This case study is the first to report survival of a male patient carrying a CASK loss-of-function mutation to adolescence and highlights that improved palliative care could extend survival. Moreover, the genomic position encoding Arg27 in CASK may possess an increased susceptibility to mutations.en
dc.description.versionPublished versionen
dc.format.extent7 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e1426 (Article number)en
dc.identifier.doihttps://doi.org/10.1002/mgg3.1426en
dc.identifier.eissn2324-9269en
dc.identifier.issn2324-9269en
dc.identifier.issue10en
dc.identifier.orcidMukherjee, Konark [0000-0002-6922-9554]en
dc.identifier.pmid32696595en
dc.identifier.urihttp://hdl.handle.net/10919/104903en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000550571900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectGenetics & Heredityen
dc.subjectCASKen
dc.subjectcerebellar hypoplasiaen
dc.subjectelectroencephalogramen
dc.subjectepileptic encephalopathyen
dc.subjectmicrocephalyen
dc.subjectHYPOPLASIAen
dc.subjectFREQUENTen
dc.subject0304 Medicinal and Biomolecular Chemistryen
dc.subject0604 Geneticsen
dc.subject1103 Clinical Sciencesen
dc.subject.meshHumansen
dc.subject.meshEpilepsyen
dc.subject.meshAbnormalities, Multipleen
dc.subject.meshGenetic Diseases, X-Linkeden
dc.subject.meshAdolescenten
dc.subject.meshMaleen
dc.subject.meshIntellectual Disabilityen
dc.subject.meshGuanylate Kinasesen
dc.subject.meshLoss of Function Mutationen
dc.titleSurvival of a male patient harboring CASK Arg27Ter mutation to adolescenceen
dc.title.serialMolecular Genetics & Genomic Medicineen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-07-02en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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