title: Renal failure associated with APECED and terminal 4q deletion: evidence of autoimmune nephropathy.
abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes' response to Candida albicans at 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH. AIRE full gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Zaidan
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bin Hussain
authors.forename: Hadeel
authors.initials: H
authors.lastname: Al-Manea
authors.forename: Hindi
authors.initials: H
authors.lastname: Al-Hindi
authors.forename: Shelley
authors.initials: S
authors.lastname: Kennedy
authors.forename: M Anwar
authors.initials: MA
authors.lastname: Iqbal
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Mojalli
authors.forename: Albandary
authors.initials: A
authors.lastname: Al-Bakheet
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
mesh_terms: D000015:Abnormalities, Multiple; D000224:Addison Disease / Q000235:genetics; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000235:genetics / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000235:genetics*; D012529:Saudi Arabia; D014157:Transcription Factors / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein