Spectrum of LMX1B mutations: from nail–patella syndrome to isolated nephropathy
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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.
KeywordsProteinuria Nephrotic syndrome Podocyte Nail–patella syndrome LMX1B LMX1B-associated nephropathy
The authors greatly acknowledge Dr Lemley for critically reading and improving this manuscript, and Dr Hisano and Dr Saisu for providing photographic images and X-rays of NPS patients. This study was supported by the Japan Renal Biopsy Registry (J-RBR), the committee of the Japanese Society of Nephrology, the Japanese Society of Pediatric Nephrology, and the Japanese Renal Pathology Society.
Compliance with ethical standards
Conflicts of interest
Motoshi Hattori has received a research grant from Astellas Pharma and Chugai Pharma. The other authors have no conflicts of interest to disclose.
Sources of support
This work was supported by Health and Labour Sciences Research Grants (H26-015; to YH, TI, SK, AA, and MH) from the Ministry of Health, Labor and Welfare of Japan.
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