Their findings might offer scientists new understanding of the disease processes in FAP, and have implications for genetic counseling, researchers said.
The study, “A Missense Variant p.Ala117Ser in the Transthyretin Gene of a Han Chinese Family with Familial Amyloid Polyneuropathy,” appeared in the journal Molecular Neurobiology.
The research team at the Third Xiangya Hospital of Central South University in China is not the first to describe the mutation — a point mutation that causes a switch in amino acids (the building blocks of proteins) in the TTR protein.
Still, it is far from common, and has mostly been described in Asian patients, often of Taiwanese descent.
The described family was also originally from Taiwan, and apparently had FAP caused by a dominant mutation. Four family members had been affected by the disease, which was characterized by bloating, alternating diarrhea and constipation, and weakness of the feet, which are typical FAP symptoms.
Focusing particularly on a man who received a liver transplant for his condition, the team analyzed the genetics of the patient and two additional family members. In addition, 200 healthy controls had been included for comparison.
The liver transplant gave researchers the opportunity to examine the patient’s liver and blood vessels leading from the digestive system to the liver. In agreement with a FAP diagnosis, they detected amyloid deposits in the blood vessel walls and in liver nerves.
Researcher detected a mutation called c.349G>T (referred to as p.Ala117Ser in the title of the study) in the affected man’s TTR gene. The mutation was also present in his son, who did not show FAP symptoms. None of the 200 controls had the same TTR gene variant.
Three different software tools for predicting the impact of gene mutations suggested that the point mutation — which caused a change in amino acids — was likely disease-causing or damaging.
The man’s symptoms were also similar to those reported in other patients with this mutation.
Earlier studies of patients with this rare mutation showed that it was linked to an earlier age at disease onset compared to the more common p.Val50Met mutation, but the study did not report on the age of the affected man or when his symptoms began.
Researchers say their findings might have implications for genetic counseling.
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