Our study narrows the AMME locus to a single point mutation in AMMECR1 that appears critical in the pathogenesis of midface hypoplasia and elliptocytosis, and contributes to early speech and language delay, hypotonia and hearing loss, and may, in addition, play a role in dysmorphism, nephrocalcinosis and submucous cleft palate. The gene discussed is AMMECR1; the disease is nephrocalcinosis.