A novel variation in the LMX1B gene with nail-patella syndrome

Nail-patella syndrome (NPS; OMIM #161200) is an autosomal dominant disorder characterized by developmental defects in dorsal limb structures, kidneys, and eyes. The incidence of NPS is attributed to variations in the LMX1B gene. In this report, we present a novel LMX1B variation identified in a Chinese family affected by NPS. The proband, a 15-year-old male, exhibited a history of proteinuria and microscopic hematuria accompanied by renal dysfunction, nail dysplasia, bilateral patellar dysplasia, bilateral shoulder and elbow joint dysplasia and iliac horns. Histological examination revealed mild glomerular lesions. Under electron microscopy, irregular thickening of the glomerular basement membrane was observed, characterized by an appearance resembling occasional electron lucent areas ("moth-eaten" appearance) and the presence of disorganized collagen fiber bundles. Pathological findings were consistent with NPS. Genetic analysis identified a novel heterozygous variant, c.791 A>C, p.(Gln264Pro), in the patient, his father and younger brother. This new variant has been annotated as potentially pathogenic according to the recommendation of the American Society for Medical Genetics and Genomics. This represents the first report of a novel variation in the LMX1B gene. These findings expand the spectrum of variations associated with LMX1B in NPS.