Familial exploration: A novel association of Thr 60Pro mutations in the Transthyretin gene with familial amyloidosis polyneuropathy

In this study, we present a rare case of familial amyloidosis polyneuropathy (FAP) caused by a novel mutation in the transthyretin protein (TTR) gene. A 40-year-old female patient presented with a complaint of numbness and weakness in both lower limbs that had persisted for a period of 18 months, accompanied by intermittent diarrhea. An analysis of her family history revealed that her father had succumbed to an instance of unexplained heart failure, while one of her siblings exhibited neurological symptoms of a comparable nature. A physical examination was conducted, which revealed sensory loss of distal symmetry, diminished tendon reflexes, and significant autonomic dysfunction. The skin biopsy revealed the presence of amyloid material deposits. Whole-exome sequencing revealed a novel mutation (c.179A>C, p.Thr60Pro), which replaces threonine with a proline at position 60 in the TTR gene. Subsequent screening revealed that other relatives carrying the same mutation also exhibited similar symptoms, thereby supporting the association between this mutation and FAP. This case underscores the significance of identifying novel TTR gene mutations, offers a novel perspective on the understanding of FAP, and posits that an early diagnosis and intervention are pivotal to enhance the prognosis.