title: Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy.
abstract: Nail-patella syndrome (NPS) is an autosomal-dominant disease caused by LMX1B mutations and is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Renal involvement is the major determinant of the prognosis for NPS. Patients often present with varying degrees of proteinuria or hematuria, and can occasionally progress to chronic renal failure. Recent genetic analysis has found that some mutations in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy). The classic term "nail-patella syndrome" would not represent disease conditions in these cases. This review provides an overview of NPS, and highlights the molecular genetics of NPS nephropathy and LMX1B-associated nephropathy. Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed. This recent progress provides insights that help to define potential targeted therapeutic strategies for LMX1B-associated diseases.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. haritay-ped@h.u-tokyo.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kitanaka
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Isojima
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ashida
authors.affiliation: Department of Pediatric Nephrology, Tokyo Women's Medical University, Sinjuku-ku, Tokyo, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hattori
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D053263:Gene Regulatory Networks / Q000235:genetics*; D050533:Glomerular Basement Membrane / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D060850:LIM-Homeodomain Proteins / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D009261:Nail-Patella Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors
keywords: LMX1B; LMX1B-associated nephropathy; Nail–patella syndrome; Nephrotic syndrome; Podocyte; Proteinuria