A trinucleotide deletion in the transthyretin gene (ΔV122) in a kindred with familial amyloidotic polyneuropathy

Tomoyuki Uemichi, Juris J. Liepnieks, Merrill Benson

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Abstract

A 63-year-old white man of Ecuadorian origin had a subarachnoid hemorrhage at age 57 followed by numbness and paresthesia in his lower extremities. He subsequently developed sexual impotence, alternating constipation and diarrhea, urinary frequency, and difficulty in walking. Rectal biopsy revealed amyloid deposits immunohistochemically reactive with antitransthyretin antisera. Direct DNA sequencing of the transthyretin gene of the patient showed a trinucleotide deletion in exon 4. This deletion resulted in the loss of one of two valines at position 121 or 122. DNA analysis on 11 family members at risk revealed four mutant gene carriers. Plasma transthyretin levels in the mutant gene carriers measured by nephelometry were very low. Peptide sequence analysis revealed that most of plasma transthyretin was normal with only a small amount of variant protein. This is the first report of a DNA deletion in the transthyretin gene. We speculate that the loss of valine in the carboxyl terminal region of the transthyretin monomer alters stability of the tetrameric protein, which leads to rapid clearance from the plasma and amyloid deposition in the tissue.

Original languageEnglish
Pages (from-to)1667-1670
Number of pages4
JournalNeurology
Volume48
Issue number6
StatePublished - Jun 1997

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Prealbumin
Polyneuropathies
Genes
Valine
Nephelometry and Turbidimetry
Mobility Limitation
Hypesthesia
Paresthesia
Protein Stability
DNA
Protein Sequence Analysis
Amyloid Plaques
Erectile Dysfunction
Subarachnoid Hemorrhage
Constipation
DNA Sequence Analysis
Amyloid
Immune Sera
Lower Extremity
Exons

ASJC Scopus subject areas

  • Neuroscience(all)

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A trinucleotide deletion in the transthyretin gene (ΔV122) in a kindred with familial amyloidotic polyneuropathy. / Uemichi, Tomoyuki; Liepnieks, Juris J.; Benson, Merrill.

In: Neurology, Vol. 48, No. 6, 06.1997, p. 1667-1670.

Research output: Contribution to journalArticle

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