Familial amyloidosis in one Chinese family: clinical, immunological, and molecular genetic analysis

Abstract

Three members of a Taiwanese kindred developed severe, systemic, early onset (<age 25 years), biopsy‐proven amyloidosis. Clinical features included upper and lower extremity sensorimotor neuropathy, abdominal pain, vomiting, corneal ulcerations, cardiomyopathy, and syncope. Immunohistochemical analysis indicated that the deposits consisted of transthyretin. Molecular genetic studies revealed a heterozygous codon 55 point mutation, resulting in a proline for leucine substitution, a mutation previously associated with aggressive familial amyloidosis in a US kindred of Dutch and German descent. The clinical courses and echocardiographic findings are typical for many types of amyloidosis; the pathologic data and genetic studies were necessary to establish a precise diagnosis.

Transthyretin Ala97Ser in Chinese–Taiwanese patients with familial amyloid polyneuropathy: Genetic studies and phenotype expression

“…This mutation was first reported in one Taiwanese patient in 1999 without mention of the detail of its characters [15]. Previous literature of the TTR mutations in Chinese was restricted in the analysis in a single family [10][11][12][13][14]. Our study is the first case series of TTR-FAP in Taiwanese-Chinese ethnics.…”

“…TTR gene analysis in several nationalities (Japanese, Portuguese, French, and British) has shown many distinguishing characteristics, including some hot-spot mutations belonging to different ethics [4][5][6][7][8][9]. In Chinese, there were only scattered reports of novel mutations, which belonged to single family separately [10][11][12][13][14]. Hot spots of TTR mutation are not identified yet.…”

Checking the conformational stability of cystatin C and its L68Q variant by molecular dynamics studies: Why is the L68Q variant amyloidogenic?

“…Similar to the L68Q cystatin C, there are known proteins with point mutation, which are engaged in the amyloid Wbril formation. Some protein mutants like V30M transthyretin (Beirao et al, 2004;Takaoka et al, 2004), D18G transthyretin (Jin et al, 2004), P55L transthyretin (Chou et al, 1997), L174S apolipoprotein AI (Mangione et al, 2001), Stop78R apolipoprotein AII (Yazaki et al, 2003), W64R lysozyme (Valleix et al, 2002) or D187N and D187Y gelsolin (Fadika and Baumann, 2002;Maury et al, 1990) are associated with hereditary amyloidosis. Since the treatment of hereditary amyloidosis greatly varies with the nature of the amyloid protein, thorough characterization of the nature of mutation is crucial for the management of the disease.…”

A novel transthyretin mutation V32A in a Chinese man with late‐onset amyloid polyneuropathy

“…Mutations other than V30M are rarer, mostly reported in a few families. There are only a few reports of transthyretin mutations in Chinese patients with FAP, namely V30A,12 F33V,18 L55P,5 T59K,11 and A97S 10. We are aware of two unrelated cases of biopsy‐proven amyloid polyneuropathy in Chinese patients harboring the A97S mutations in Singapore (unpublished).…”