title: Severe XLP Phenotype Caused by a Novel Intronic Mutation in the SH2D1A Gene.
abstract: We describe here a novel c.137 + 5G > A intronic mutation in the SH2D1A gene of the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in association with Epstein-Barr virus (EBV)-induced fatal infectious mononucleosis (FIM) in an 8-year-old male patient and his 3-year-old step brother. The mother and the maternal grandmother of the boys are healthy and heterozygous for this sequence variant. Genetic sequencing of blood-cell-derived cDNA in the younger patient revealed a 22 bp deletion in the SH2D1A cDNA. Immunoblot and flow cytometry analysis performed in this younger patient showed the lack of SAP protein expression in peripheral blood lymphocytes. These data suggest that the novel c.137 + 5G > A mutation results in loss of function of SAP protein and leads to typical X-linked lymphoproliferative disease phenotype. We propose that intron 1 and the c.137 + 5G may be the most frequent intronic hot spot for SH2D1A splicing mutation.
authors.affiliation: Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Tóth
authors.affiliation: Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Soltész
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Gyimesi
authors.affiliation: Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Csorba
authors.affiliation: Institute of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Á
authors.initials: Á
authors.lastname: Veres
authors.affiliation: Institute of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Á
authors.initials: Á
authors.lastname: Lányi
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Kovács
authors.affiliation: Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Maródi
authors.affiliation: Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98, 4012, Debrecen, Hungary. melinda.erdos@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Erdős
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000235:genetics; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007438:Introns; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
chemical_list: D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
keywords: SH2D1A; XLP; novel intronic mutation