Pseudoxanthoma Elasticum
In a patient with autosomal recessive pseudoxanthoma elasticum (PXE; 264800), Le Saux et al. (2000) identified a C-to-T transition at nucleotide 3940 of the ABCC6 gene, resulting in an arg-to-trp substitution at codon 1314 (R1314W). This mutation was found in homozygosity in one family.
Generalized Arterial Calcification of Infancy 2
In a 5-year-old boy with generalized arterial calcification of infancy (GACI2; 614473), Nitschke et al. (2012) identified homozygosity for the R1314W mutation. The boy was born as the first of dizygotic twins, and his twin brother was unaffected. The patient had calcification of the aorta and pulmonary, coronary, and renal arteries as well as other arteries, and stippled calcifications of proximal epiphyses of humeri, femora, pelvic cartilage, larynx, and mandible. He had severely decreased biventricular systolic function, marked cardiomegaly, and severe mitral insufficiency, as well as hypertension and respiratory insufficiency. Cerebral MRI revealed diffuse white matter disease, with cystic encephalomalacia, and laboratory analysis showed hyperbilirubinemia, anemia, and thrombocytopenia. Nitschke et al. (2012) also identified the R1314W mutation in compound heterozygosity in 2 unrelated GACI patients, a French female infant who died at 6 weeks of age and also carried an R1141X mutation (603234.0001), and an Afro-Caribbean male infant who died at 8 weeks of age with generalized arterial stenosis, myocardial infarction, and hypertension and also carried a 1-bp insertion (450insC; 603234.0028) in exon 4 of the ABCC6 gene, predicted to result in a premature stop codon and a truncated protein. In addition, in a 3-year-old South African girl with GACI, Nitschke et al. (2012) identified only a heterozygous R1314W mutation, but noted that mutations in regulatory untranslated regions of ABCC6 might not have been detected by their technique. In the South African child, onset of symptoms occurred at 2.5 years of age, and included calcification of the aorta, spleen, and pancreas, nephrocalcinosis, failure to thrive, hypertension, and heart failure.
