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Segmental and total uniparental isodisomy (UPiD) as a disease mechanism in autosomal recessive lysosomal disorders: evidence from SNP arrays

2019-06Journal article Open access
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dc.contributor.authorLabrijn-Marks, Ineke
dc.contributor.authorSomers-Bolman, Galhana M.
dc.contributor.authorIn ’t Groen, Stijn L. M.
dc.contributor.authorHoogeveen-Westerveld, Marianne
dc.contributor.authorKroos, Marian A.
dc.contributor.authorAla-Mello, Sirpa
dc.contributor.authorAmaral, Olga
dc.contributor.authorMiranda, Clara sa
dc.contributor.authorMavridou, Irene
dc.contributor.authorMichelakakis, Helen
dc.contributor.authorNaess, Karin
dc.contributor.authorVerheijen, Frans W.
dc.contributor.authorHoefsloot, Lies H.
dc.contributor.authorDijkhuizen, Trijnie
dc.contributor.authorBenjamins, Marloes
dc.contributor.authorvan den Hout, Hannerieke J.M.
dc.contributor.authorvan der Ploeg, Ans T.
dc.contributor.authorPijnappel, W. W. M. Pim
dc.contributor.authorSaris, Jasper J.
dc.contributor.authorHalley, Dicky J.
dc.date.accessioned2020-04-29T05:57:33Z
dc.date.available2020-04-29T05:57:33Z
dc.date.issued2019-06
dc.descriptionCollaboration from previous work institution.pt_PT
dc.descriptionFree PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30737479/pt_PT
dc.description.abstractAnalyses in our diagnostic DNA laboratory include genes involved in autosomal recessive (AR) lysosomal storage disorders such as glycogenosis type II (Pompe disease) and mucopolysaccharidosis type I (MPSI, Hurler disease). We encountered 4 cases with apparent homozygosity for a disease-causing sequence variant that could be traced to one parent only. In addition, in a young child with cardiomyopathy, in the absence of other symptoms, a diagnosis of Pompe disease was considered. Remarkably, he presented with different enzymatic and genotypic features between leukocytes and skin fibroblasts. All cases were examined with microsatellite markers and SNP genotyping arrays. We identified one case of total uniparental disomy (UPD) of chromosome 17 leading to Pompe disease and three cases of segmental uniparental isodisomy (UPiD) causing Hurler-(4p) or Pompe disease (17q). One Pompe patient with unusual combinations of features was shown to have a mosaic segmental UPiD of chromosome 17q. The chromosome 17 UPD cases amount to 11% of our diagnostic cohort of homozygous Pompe patients (plus one case of pseudoheterozygosity) where segregation analysis was possible. We conclude that inclusion of parental DNA is mandatory for reliable DNA diagnostics. Mild or unusual phenotypes of AR diseases should alert physicians to the possibility of mosaic segmental UPiD. SNP genotyping arrays are used in diagnostic workup of patients with developmental delay. Our results show that even small Regions of Homozygosity that include telomeric areas are worth reporting, regardless of the imprinting status of the chromosome, as they might indicate segmental UPiD.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEur J Hum Genet. 2019 Jun;27(6):919-927. doi: 10.1038/s41431-019-0348-y. Epub 2019 Feb 8pt_PT
dc.identifier.doi10.1038/s41431-019-0348-ypt_PT
dc.identifier.issn1018-4813
dc.identifier.urihttp://hdl.handle.net/10400.18/6554
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Nature/ European Society of Human Geneticspt_PT
dc.relation.publisherversionhttps://www.nature.com/articles/s41431-019-0348-ypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectLysiosomal Diseasespt_PT
dc.subjectHuman Geneticspt_PT
dc.subjectGenetic Diagnosispt_PT
dc.subjectUniparental Disomypt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenética Humanapt_PT
dc.titleSegmental and total uniparental isodisomy (UPiD) as a disease mechanism in autosomal recessive lysosomal disorders: evidence from SNP arrayspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage927pt_PT
oaire.citation.issue6pt_PT
oaire.citation.startPage919pt_PT
oaire.citation.titleEuropean Journal of Human Geneticspt_PT
oaire.citation.volume27pt_PT
person.familyNameAmaral
person.givenNameOlga
person.identifier.ciencia-id6F1F-54A3-BBB9
person.identifier.orcid0000-0002-3478-2122
person.identifier.scopus-author-id7004054964
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication8c7fb04a-80c0-4dd7-b3c5-682f6d25662b
relation.isAuthorOfPublication.latestForDiscovery8c7fb04a-80c0-4dd7-b3c5-682f6d25662b

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