COL4A1 Mutations Implicated in Proposed New Syndrome
They may explain cause of hereditary angiopathy, nephropathy, aneurysms and muscle cramps
WEDNESDAY, Dec. 26 (HealthDay News) -- Mutations in the COL4A1 gene may be the cause of a proposed new syndrome: hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC), according to research published in the Dec. 27 issue of the New England Journal of Medicine.
Emmanuelle Plaisier, M.D., of the Universite Pierre et Marie Curie in Paris, France, and colleagues studied subjects from three families with autosomal dominant HANAC and characterized their renal and extra-renal phenotypes. They also performed linkage studies involving microsatellite markers flanking the COL4A1-COL4A2 locus, followed by sequence analysis of COL4A1 complementary DNA derived from subjects' skin fibroblasts.
The researchers identified three glycine mutations of the COL4A1 gene located in exons 24 and 25. The gene COL4A1 encodes procollagen type IV α1. The clinical picture for afflicted families included hematuria and large, bilateral renal cysts. Complex basement-membrane defects were seen in both kidney and skin upon histologic examination.
"The systemic angiopathy of the HANAC syndrome appears to affect both small vessels and large arteries," the authors state. "Diagnosis of the HANAC syndrome could be considered in families with unexplained, autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps; such consideration would involve funduscopic examination and a search for COL4A1 mutations."