title: Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa.
abstract: Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient's renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.
authors.affiliation: Department of Pediatrics, Kitano Hospital, Tazuke Kofukai Medical Institute, 2-4-20 Ohgimachi, Osaka, 530-8480, Japan. d-hata@kitano-hp.or.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hata
authors.forename: Maki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Seto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kadota
authors.forename: Eri
authors.initials: E
authors.lastname: Muso
authors.forename: Kosho
authors.initials: K
authors.lastname: Takasu
authors.forename: Aoi
authors.initials: A
authors.lastname: Nakano
authors.forename: Katsuto
authors.initials: K
authors.lastname: Tamai
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.forename: Kayano
authors.initials: K
authors.lastname: Moriyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D001485:Basement Membrane / Q000378:metabolism; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007684:Kidney Tubules / Q000378:metabolism; D007797:Laminin / Q000032:analysis* / Q000235:genetics; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis; D011507:Proteinuria
chemical_list: D007797:Laminin; D020033:Protein Isoforms