Faith Pangilinan, David Watkins, David Bernard, Yue Chen, Ningzheng Dong, Qingyu Wu, Hatice Ozel-Abaan, Manjit Kaur, Michele Caggana, Mark Morrissey, Marilyn L Browne, James L Mills, Carol Van Ryzin, Oleg Shchelochkov, Jennifer Sloan, Charles P Venditti, Kyriakie Sarafoglou, David S Rosenblatt, Denise M Kay, Lawrence C Brody
The biological and clinical significance of the p.E88del variant in the transcobalamin receptor, CD320, is unknown. This allele is annotated in ClinVar as likely benign, pathogenic, and of uncertain significance. To determine functional consequence and clinical relevance of this allele, we employed cell culture and genetic association studies. Fibroblasts from 16 CD320 p.E88del homozygotes exhibited reduced binding and uptake of cobalamin. Complete ascertainment of newborns with transiently elevated C3 (propionylcarnitine) in New York State demonstrated that homozygosity for CD320 p...
April 2022: American Journal of Medical Genetics. Part A