Missense mutations in COL4A5 or COL4A6 genes may cause cerebrovascular fibromuscular dysplasia: Case report and literature review

INTRODUCTION: Fibromuscular dysplasia (FMD) is a rare and controversial disease that is seldom associated with genes. Here, we report the discovery of 2 missense mutations in COL4A5 and COL4A6 that may be risk factors for causing cerebrovascular FMD. We performed high-throughput sequencing on a patient with FMD and her probable healthy daughter, then annotated the frequency of a variant in a control or general population and assessed its deleterious effects according to published guidelines. CONCLUSIONS: We identified missense mutations in COL4A5 (exon43:c.C3940 > T:p.P1314S) and COL4A6 (exon36:c.C3538 > T:p.P1180S) from the proband and her daughter. Sanger sequencing revealed that these probable causal variants were passed to her from her mother. The two missense mutations may have complex functional effects on the integrity of the cerebral vessel walls, including modulating collagens and promoting angiogenesis expression, may be responsible for cerebrovascular FMD.