Spectrum of LMX1B mutations: from nail–patella syndrome to isolated nephropathy

• Published in: Pediatric nephrology (Berlin, West) West), 2017-10, Vol.32 (10), p.1845-1850
• Main Authors: Harita, Yutaka, Kitanaka, Sachiko, Isojima, Tsuyoshi, Ashida, Akira, Hattori, Motoshi
• Format: Article
• Language: English
• Subjects: Animals; Care and treatment; Disease Models, Animal; DNA Mutational Analysis; Dysplasia; Elbow; Gene mutation; Gene Regulatory Networks - genetics; Genetic analysis; Genetic aspects; Glomerular Basement Membrane - pathology; Hematuria; High-Throughput Nucleotide Sequencing; Homeobox; Humans; Kidney diseases; Kidney Diseases - diagnosis; Kidney Diseases - drug therapy; Kidney Diseases - genetics; Kidney Diseases - pathology; Kidneys; LIM-Homeodomain Proteins - genetics; Medicine; Medicine & Public Health; Molecular Targeted Therapy - methods; Mutation; Nail-patella syndrome; Nail-Patella Syndrome - diagnosis; Nail-Patella Syndrome - drug therapy; Nail-Patella Syndrome - genetics; Nails (Anatomy); Nephrology; Nephropathy; Patella; Pediatrics; Prognosis; Proteinuria; Renal failure; Review; Transcription Factors - genetics; Urology
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-016-3462-x

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.