Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity, Primordial Dwarfism, and Neurological Abnormalities

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dc.contributor.authorJspeert, Hanna I.
dc.contributor.authorWarris, Adilia
dc.contributor.authorvan der Flier, Michiel
dc.contributor.authorReisli, Ismail
dc.contributor.authorKeles, Sevgi
dc.contributor.authorChishimba, Sandra
dc.contributor.authorvan Dongen, Jacques J. M.
dc.date.accessioned2024-02-23T12:11:09Z
dc.date.available2024-02-23T12:11:09Z
dc.date.issued2013
dc.departmentNEÜen_US
dc.description.abstractDNA double-strand break repair via non-homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme radiosensitivity, severe dysmaturity, corpus callosum agenesis, polysyndactily, dysmorphic appearance, and erythema, which are suggestive of a new type of NHEJ deficiency. We identified two heterozygous mutations in LIG4. The p.S205LfsX29 mutation results in lack of the nuclear localization signal and appears to be a null mutation. The second mutation p.K635RfsX10 lacks the C-terminal region responsible for XRCC4 binding and LIG4 stability and activity, and therefore this mutant might be a null mutation as well or have very low residual activity. This is remarkable since Lig4 knockout mice are embryonic lethal and so far in humans no complete LIG4 deficiencies have been described. This case broadens the clinical spectrum of LIG4 deficiencies. Published 2013 Wiley Periodicals, Inc.en_US
dc.description.sponsorshipSophia Kinderziekenhuis Fonds [589, 91712323]en_US
dc.description.sponsorshipContract grant sponsor: Sophia Kinderziekenhuis Fonds (grant 589 and Vidi grant 91712323).en_US
dc.identifier.doi10.1002/humu.22436
dc.identifier.endpage1614en_US
dc.identifier.issn1059-7794
dc.identifier.issn1098-1004
dc.identifier.issue12en_US
dc.identifier.pmid24027040en_US
dc.identifier.scopus2-s2.0-84887607453en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1611en_US
dc.identifier.urihttps://doi.org/10.1002/humu.22436
dc.identifier.urihttps://hdl.handle.net/20.500.12452/10568
dc.identifier.volume34en_US
dc.identifier.wosWOS:000326864200004en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofHuman Mutationen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectLig4en_US
dc.subjectImmunodeficiencyen_US
dc.subjectPrimordial Dwarfismen_US
dc.subjectNon-Homologous End Joiningen_US
dc.subjectNhejen_US
dc.titleClinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity, Primordial Dwarfism, and Neurological Abnormalitiesen_US
dc.typeArticleen_US

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