Ann Lab Med.  2016 May;36(3):259-262. 10.3343/alm.2016.36.3.259.

The First Korean Family With Hereditary Gelsolin Amyloidosis Caused by p.D214Y Mutation in the GSN Gene

• Park KJ
• Park JH
• Park JH
• Cho EB
• Kim BJ
• Kim JW

• KMID: 2373537
• DOI: http://doi.org/10.3343/alm.2016.36.3.259

Abstract

Hereditary gelsolin amyloidosis (HGA) is an autosomal dominant hereditary disease characterized by corneal lattice dystrophy, peripheral neuropathy, and cutis laxa. So far, no Korean patients with HGA have been reported. A 58-yr-old man presented with involuntary facial twitching, progressive bilateral facial weakness, and tongue atrophy. His mother, maternal uncle, two sisters, and son suffered from the same symptoms. Electrophysiological studies revealed signs of chronic denervation in the cervical and lumbar regions, mild sympathetic autonomic dysfunction, and bilateral facial nerve dysfunction. Diagnostic whole-exome sequencing (WES) revealed a p.D214Y heterozygous mutation in the gelsolin gene in affected members. We present the first report of a Korean family with HGA diagnosed by WES. WES facilitated a clinical diagnosis of HGA in patients with undiagnosed neuropathies.

Keyword

Hereditary gelsolin amyloidosis (HGA); Gelsolin; Neuropathy; Whole-exome sequencing (WES)

MeSH Terms

Amyloidosis, Familial/diagnosis/*genetics
Asian Continental Ancestry Group/*genetics
Base Sequence
DNA Mutational Analysis
Gelsolin/*genetics
Genotype
Heterozygote
Humans
Male
Middle Aged
Pedigree
Polymorphism, Single Nucleotide
Republic of Korea
Gelsolin

Figure

• 

  Fig. 1 A Korean family with hereditary gelsolin amyloidosis. (A) Pedigree of the family. The proband is represented by the arrow. Affected individuals are indicated by solid symbols. Germline DNA was obtained from four individuals (III:2, III:3, III:4, and III:5), including the proband. G, reference allele; T, mutant allele. (B) Validation of the mutation by Sanger sequencing. The p.D214Y mutation was identified in a symptomatic sister (III:3) and in the proband (III:5). Sequences identical to the reference genotype were observed in two asymptomatic members (III:2 and III:4) of the family.

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