Shteyer et al reports correlative evidence of a truncating mutation of nNOSα in 2 probands (siblings) of achalasia.1 This excellent study leaves scope for additional discussion. Achalasia results from prejunctional defects of evoked nitric oxide (NO) synthesis or postjunctional failure of signal transduction.2 In the present study, the affected children exhibits a nonsense mutation in which amino acids beyond 1202 of nNOSC-terminal is deleted.1 The authors expressed the truncated enzyme (nNOSdel1203-1434) in vitro and demonstrated absent NO production.