We introduced a BTHS patient’s point mutation (TAZD75H) into the mouse Tafazzin enzyme’s critical acyltransferase site using CRISPR/Cas9-mediated genome editing, resulting in a patient-tailored point mutant knock-in BTHS model (TazD75H) that expresses a stable mutant TazD75H protein lacking transacylase activity. The gene discussed is TAFAZZIN; the disease is Barth syndrome.