A Missense Variant p.Ala117Ser in the Transthyretin Gene of a Han Chinese Family with Familial Amyloid Polyneuropathy.

Familial amyloid polyneuropathy (FAP) is a dominantly inherited disorder. This study aims to explore the genetic features of a Han Chinese family with FAP, characterized by bloating, alternating diarrhea and constipation, and weakness in his feet. Amyloid presented histologically in the vessel walls of hepatic portal area and nerves of the surgically excised liver specimens from the proband by hematoxylin and eosin staining. Amyloid deposition was further confirmed with Congo red treatment. A c.349G>T transversion (p.Ala117Ser) in TTR gene exon 4 was identified in the proband with typical autonomic neuropathy and peripheral motor neuropathy, as well as in his asymptomatic son. The variant was not detected in 200 normal ethnically matched controls. These findings provide new insights into FAP cause and diagnosis and have implications for genetic counseling.