Diagnosis of MCTD should be considered in patients having positive anti-U1 RNP antibodies and presenting clinical manifestations such as Raynaud's phenomenon and diffuse hand edema (“puffy hands”); these patients, however, do not meet all the diagnostic criteria of other CTDs (SSc, PM and SLE) [19]. The gene discussed is RNPC3; the disease is systemic lupus erythematosus.