Identification of a novel TTR Gly67Glu mutant and the first case series of familial transthyretin amyloidosis in Hong Kong Chinese.
Familial transthyretin amyloidosis (ATTR), caused by mutant transthyretin deposition, is mainly characterized by peripheral neuropathy, autonomic dysfunction, and cardiomyopathy. There are few reports among the Chinese population. We previously described the TTR mutation (Val30Ala) in the first Hong Kong Chinese family with ATTR. In this study, we report the progress of this family and describe another three unrelated Chinese kinships newly diagnosed with ATTR. The second proband presented mainly with peripheral neuropathy, and genetic analysis of the TTR gene showed alanine-to-serine substitution at amino acid 97. The third proband complained of autonomic dysfunction, and a novel missense mutation of glycine-to-glutamate substitution at amino acid 67 was found. The fourth patient presented with peripheral neuropathy and diastolic cardiomyopathy with the mutation threonine-to-lysine at codon 59. Diagnosis was delayed for more than 2 years. We performed DNA analysis in 46 subjects and detected a total of 21 patients, including the four probands, affected with ATTR, 15 of whom were still at a symptom-free stage at the time of writing. We conclude that ATTR remains largely underdiagnosed in the Chinese population. A high clinical suspicion is crucial for a timely diagnosis and can thus lead to a significant decrease in morbidity and mortality.
Mak
Chloe M
CM
Division of Clinical Biochemistry, Queen Mary Hospital, Hong Kong SAR, China.
Kwong
Yok-Lam
YL
Lam
Ching-Wan
CW
Chan
See-Ching
SC
Lo
Chung-Mau
CM
Fan
Sheung-Tak
ST
Chang
Chee-My
CM
Lau
Yuk-Kwong
YK
U
Lok-Sun
LS
Tam
Sidney
S
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D028226:Amyloidosis, Familial / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006723:Hong Kong; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011228:Prealbumin / Q000235:genetics*
D011228:Prealbumin; D018698:Glutamic Acid; D005998:Glycine