A homozygous R148W mutation in Semaphorin 7A causes progressive familial intrahepatic cholestasis.

ABSTRACT: Semaphorin 7A (SEMA7A) is a membrane-bound protein that involves axon growth and other biological processes. SEMA7A mutations are associated with vertebral fracture and Kallmann syndrome. Here, we report a case with a mutation in SEMA7A that displays familial cholestasis. WGS reveals a SEMA7A^R148W homozygous mutation in a female child with elevated levels of serum ALT, AST, and total bile acid (TBA) of unknown etiology. This patient also carried a SLC10A1^S267F allele, but Slc10a1^S267F homozygous mice exhibited normal liver function. Similar to the child, Sema7a^R145W homozygous mice displayed elevated levels of serum ALT, AST, and TBA. Remarkably, liver histology and LC-MS/MS analyses exhibited hepatocyte hydropic degeneration and increased liver

SUBMITTER: Pan Q 

PROVIDER: S-EPMC8573601 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature