title: Skin lesions in a boy with X-linked lymphoproliferative disorder: comparison of 5 SH2D1A deletion cases.
abstract: SH2D1A gene defects are the cause of X-linked lymphoproliferative disorder (XLP-1), a rare condition characterized by severe immune dysregulation. We present a patient lacking the typical symptoms of XLP-1, but experiencing a severe unusual skin condition encompassing features of dermatosclerosis and vesiculobullous skin disease. A maternal cousin of the patient was diagnosed with XLP-1 and found to carry a deletion of the SH2D1A gene. SH2D1A deletion was also identified in our patient, which offered a possible explanation for his skin symptoms. Subsequent analysis showed that the deletion in both cousins was identical and involved the whole SH2D1A gene and a part of the adjacent ODZ1 gene. High phenotypic variability of XLP-1 observed in this family prompted us to analyze the genotype-phenotype correlation of 2 different-sized deletions involving SH2D1A and ODZ1 in 5 patients from 2 families, and we report the clinical and laboratory data on these individuals. Our findings illustrate the wide clinical variability of XLP-1, both inter- and intrafamilial, which may complicate the diagnosis of this condition. The comparison of phenotypes of our patients argues against a strong involvement of the ODZ1 gene in the skin disorder and other symptoms observed in our index patient. His hitherto not described severe skin condition extends the phenotypic range of XLP-1.
authors.affiliation: Department of Pediatric Hematology and Oncology, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ester
authors.initials: E
authors.lastname: Mejstríková
authors.forename: Ales
authors.initials: A
authors.lastname: Janda
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hrusák
authors.forename: Hana
authors.initials: H
authors.lastname: Bucková
authors.forename: Markéta
authors.initials: M
authors.lastname: Vlcková
authors.forename: Miroslava
authors.initials: M
authors.lastname: Hancárová
authors.forename: Tomás
authors.initials: T
authors.lastname: Freiberger
authors.forename: Barbora
authors.initials: B
authors.lastname: Ravcuková
authors.forename: Karel
authors.initials: K
authors.lastname: Vesely
authors.forename: Lenka
authors.initials: L
authors.lastname: Fajkusová
authors.forename: Lenka
authors.initials: L
authors.lastname: Kopecková
authors.forename: David
authors.initials: D
authors.lastname: Sumerauer
authors.forename: Edita
authors.initials: E
authors.lastname: Kabícková
authors.forename: Anna
authors.initials: A
authors.lastname: Sedivá
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Sedlácek
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D015897:Comorbidity; D005091:Exons / Q000235:genetics; D054747:Histiocytic Sarcoma / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D007244:Infectious Mononucleosis / Q000175:diagnosis / Q000628:therapy; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008137:Longitudinal Studies; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins; D036102:Peripheral Blood Stem Cell Transplantation; D010641:Phenotype; D012594:Scleroderma, Localized / Q000175:diagnosis / Q000235:genetics*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D012872:Skin Diseases, Vesiculobullous / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D019063:Tenascin
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D019063:Tenascin; C120530:teneurin-1