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: B Tóth, B Soltész, E Gyimesi, G Csorba, Á Veres, Á Lányi, G Kovács, L Maródi, M Erdős
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 35 Issue 1 Pg. 26-31 (Jan 2015) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 25491288 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Intracellular Signaling Peptides and Proteins
• SH2D1A protein, human
• Signaling Lymphocytic Activation Molecule Associated Protein

Topics

• Base Sequence
• Child
• Child, Preschool
• DNA, Complementary (genetics)
• Epstein-Barr Virus Infections (etiology, genetics)
• Female
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Introns
• Lymphoproliferative Disorders (complications, genetics)
• Male
• Mutation
• Pedigree
• Phenotype
• Sequence Deletion
• Signaling Lymphocytic Activation Molecule Associated Protein