Hofstra et al. (1999) described a patient with skip-lesions Hirschsprung disease, cardiac defects (ductus arteriosus, small subaortic ventricular septal defect, and small atrial septal defect), craniofacial abnormalities (cupped ears which were immature and posteriorly rotated and small nose ... Hofstra et al. (1999) described a patient with skip-lesions Hirschsprung disease, cardiac defects (ductus arteriosus, small subaortic ventricular septal defect, and small atrial septal defect), craniofacial abnormalities (cupped ears which were immature and posteriorly rotated and small nose with a high bridge and bulbous tip), other dysmorphic features (tapered fingers with hyperconvex nails, a single left palmar crease, contractures at the interphalangeal joint of the thumbs, proximal interphalangeal joints of the fingers bilaterally, and micropenis), and autonomic dysfunction (episodes of severe agitation in association with significant tachycardia, hypertension, and core temperatures as high as 40.5 degrees C, and status epilepticus). The patient had a normal karyotype without a 22q11 deletion.
By screening all 19 exons of the ECE1 gene in a patient with Hirschsprung disease, cardiac defects, and autonomic dysfunction, Hofstra et al. (1999) identified a heterozygous C-to-T transition, resulting in the substitution of cysteine for arginine at ... By screening all 19 exons of the ECE1 gene in a patient with Hirschsprung disease, cardiac defects, and autonomic dysfunction, Hofstra et al. (1999) identified a heterozygous C-to-T transition, resulting in the substitution of cysteine for arginine at position 742 (R742C; 600423.0001). The patient's parents were not available for testing. Amino acid position 742 is in the vicinity of the active site of ECE1 (Valdenaire et al., 1995). Hofstra et al. (1999) suggested that the mutation was responsible for, or at least contributed to, the phenotype of the patient in view of the function of ECE1 during murine development suggested by mouse models, the overlap in phenotypic features of these mouse models and those of the patient, and the functional consequences of the mutation on enzyme activity. The mutation was thought to lead to the phenotype by resulting in reduced levels of EDN1 and EDN3.