X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa

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dc.contributor.authorPienaar, Sandraen_ZA
dc.contributor.authorEley, Brianen_ZA
dc.contributor.authorHughes, Janeen_ZA
dc.contributor.authorHenderson, Howarden_ZA
dc.date.accessioned2015-10-12T11:01:07Z
dc.date.available2015-10-12T11:01:07Z
dc.date.issued2003en_ZA
dc.description.abstractBACKGROUND:The objective of this study was to describe the clinical and molecular features of the first South African family with X-linked hyper-IgM syndrome (HIGM1). METHODS: Diagnoses were based on immunoglobulin results and the absence of CD40 ligand (CD40L) expression on activated T-cells. Complete molecular characterisation involved CD40L cDNA sequencing, and genomic DNA analysis by polymerase chain reaction amplification, restriction enzyme digestion and sequencing. A PCR-based diagnostic assay was established for carrier detection and prenatal diagnosis in this family. RESULTS: There were originally six children, three males and three females. The eldest boy died after being diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder was diagnosed in the second eldest boy at the age of 5 years, after failing to detect CD40L expression on his activated T-cells. A deficiency of CD40L was also confirmed in the youngest male at the age of 5 years. Both younger brothers have since died of infections relating to HIGM1. Molecular investigation showed that exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA analysis identified a 1.5 kilobase deletion, spanning exon 3 and including extended flanking intronic sequence. Carrier status in the mother was confirmed by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was deferred because they were below the legal consenting age of 18 years. A PCR-based assay for genomic DNA was established for easy identification of female carriers and affected males in the future. CONCLUSIONS: This study confirmed the diagnosis of HIGM1 in the first South African family to be investigated and identified a novel mutation in the CD40L gene.en_ZA
dc.identifier.apacitationPienaar, S., Eley, B., Hughes, J., & Henderson, H. (2003). X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa. <i>BMC Pediatrics</i>, http://hdl.handle.net/11427/14214en_ZA
dc.identifier.chicagocitationPienaar, Sandra, Brian Eley, Jane Hughes, and Howard Henderson "X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa." <i>BMC Pediatrics</i> (2003) http://hdl.handle.net/11427/14214en_ZA
dc.identifier.citationPienaar, S., Eley, B. S., Hughes, J., & Henderson, H. E. (2003). X-linked hyper IgM (HIGM1) in an African kindred: the first report from South Africa. BMC pediatrics, 3(1), 12.en_ZA
dc.identifier.ris TY - Journal Article AU - Pienaar, Sandra AU - Eley, Brian AU - Hughes, Jane AU - Henderson, Howard AB - BACKGROUND:The objective of this study was to describe the clinical and molecular features of the first South African family with X-linked hyper-IgM syndrome (HIGM1). METHODS: Diagnoses were based on immunoglobulin results and the absence of CD40 ligand (CD40L) expression on activated T-cells. Complete molecular characterisation involved CD40L cDNA sequencing, and genomic DNA analysis by polymerase chain reaction amplification, restriction enzyme digestion and sequencing. A PCR-based diagnostic assay was established for carrier detection and prenatal diagnosis in this family. RESULTS: There were originally six children, three males and three females. The eldest boy died after being diagnosed with hypogammaglobulinaemia, before HIGM1 was considered. This disorder was diagnosed in the second eldest boy at the age of 5 years, after failing to detect CD40L expression on his activated T-cells. A deficiency of CD40L was also confirmed in the youngest male at the age of 5 years. Both younger brothers have since died of infections relating to HIGM1. Molecular investigation showed that exon 3 was deleted from the CD40L mRNA of the affected males. Genomic DNA analysis identified a 1.5 kilobase deletion, spanning exon 3 and including extended flanking intronic sequence. Carrier status in the mother was confirmed by RT-PCR of her CD40L mRNA. Genetic analysis of the three female children was deferred because they were below the legal consenting age of 18 years. A PCR-based assay for genomic DNA was established for easy identification of female carriers and affected males in the future. CONCLUSIONS: This study confirmed the diagnosis of HIGM1 in the first South African family to be investigated and identified a novel mutation in the CD40L gene. DA - 2003 DB - OpenUCT DO - 10.1186/1471-2431-3-12 DP - University of Cape Town J1 - BMC Pediatrics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2003 T1 - X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa TI - X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa UR - http://hdl.handle.net/11427/14214 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14214
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2431-3-12
dc.identifier.vancouvercitationPienaar S, Eley B, Hughes J, Henderson H. X-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africa. BMC Pediatrics. 2003; http://hdl.handle.net/11427/14214.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Paediatrics and Child Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Pediatricsen_ZA
dc.source.urihttp://www.biomedcentral.com/1471-2431en_ZA
dc.titleX-linked Hyper IgM (HIGM1) in an African kindred: the first report from South Africaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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