A transthyretin mutation (Tyr78Phe) associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis

Nadine Magy, Juris J. Liepnieks, Helder Gil, Bernadette Kantelip, Jean Louis Dupond, Barbara Kluve-Beckerman, Merrill D. Benson

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. More than 80 transthyretin (TTR) mutations have been described, most associated with amyloidosis. Peripheral neuropathy is the most common clinical presentation in TTR amyloidosis although the carpal tunnel syndrome (CTS) may be the first symptom and skin can be involved, as transthyretin amyloidosis is a systemic disease. Case report. The 78 year-old proband, belonging to a French family of Italian origin, presented with a 5 year history of peripheral neuropathy in the lower extremities. However, 15 years earlier he had had surgery for bilateral CTS. Amyloidosis was diagnosed on salivary gland and skin biopsies. Immunohistochemistry on skin biopsy was positive using anti-TTR. The proband has 10 siblings, 5 have CTS. Methods. SSCP and direct sequencing of exons 2, 3, and 4 of the TTR gene were done on DNA from the proband and his brother who had had CTS. To confirm the mutation a PCR-IMRA was done. Results. SSCP analysis of TTR exons 2, 3, and 4 did not suggest a mutation. Sequence analysis of TTR exon 3 revealed heterozygosity m both subjects for a single base-pair transversion from A to T in codon 78 (TAC→TTC) indicating a tyrosine to phenylalanine change. The mutation was confirmed by PCR-IMRA. Conclusion. This TTR mutation (Tyr78Phe) is associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. It is also associated with late onset of the disease.

Original languageEnglish (US)
Pages (from-to)29-33
Number of pages5
JournalAmyloid
Volume10
Issue number1
DOIs
StatePublished - Mar 2003

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Prealbumin
Carpal Tunnel Syndrome
Peripheral Nervous System Diseases
Amyloidosis
Skin
Mutation
Single-Stranded Conformational Polymorphism
Exons
Biopsy
Polymerase Chain Reaction
Salivary Glands
Phenylalanine
Codon
Base Pairing
Sequence Analysis
Tyrosine
Lower Extremity
Immunohistochemistry
DNA
Genes

Keywords

  • Carpal tunnel syndrome
  • Familial amyloidosis
  • Polyneuropathy
  • Skin amyloidosis
  • Transthyretin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

A transthyretin mutation (Tyr78Phe) associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. / Magy, Nadine; Liepnieks, Juris J.; Gil, Helder; Kantelip, Bernadette; Dupond, Jean Louis; Kluve-Beckerman, Barbara; Benson, Merrill D.

In: Amyloid, Vol. 10, No. 1, 03.2003, p. 29-33.

Research output: Contribution to journalArticle

Magy, Nadine ; Liepnieks, Juris J. ; Gil, Helder ; Kantelip, Bernadette ; Dupond, Jean Louis ; Kluve-Beckerman, Barbara ; Benson, Merrill D. / A transthyretin mutation (Tyr78Phe) associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. In: Amyloid. 2003 ; Vol. 10, No. 1. pp. 29-33.
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abstract = "Background. More than 80 transthyretin (TTR) mutations have been described, most associated with amyloidosis. Peripheral neuropathy is the most common clinical presentation in TTR amyloidosis although the carpal tunnel syndrome (CTS) may be the first symptom and skin can be involved, as transthyretin amyloidosis is a systemic disease. Case report. The 78 year-old proband, belonging to a French family of Italian origin, presented with a 5 year history of peripheral neuropathy in the lower extremities. However, 15 years earlier he had had surgery for bilateral CTS. Amyloidosis was diagnosed on salivary gland and skin biopsies. Immunohistochemistry on skin biopsy was positive using anti-TTR. The proband has 10 siblings, 5 have CTS. Methods. SSCP and direct sequencing of exons 2, 3, and 4 of the TTR gene were done on DNA from the proband and his brother who had had CTS. To confirm the mutation a PCR-IMRA was done. Results. SSCP analysis of TTR exons 2, 3, and 4 did not suggest a mutation. Sequence analysis of TTR exon 3 revealed heterozygosity m both subjects for a single base-pair transversion from A to T in codon 78 (TAC→TTC) indicating a tyrosine to phenylalanine change. The mutation was confirmed by PCR-IMRA. Conclusion. This TTR mutation (Tyr78Phe) is associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. It is also associated with late onset of the disease.",
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AU - Magy, Nadine

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AU - Gil, Helder

AU - Kantelip, Bernadette

AU - Dupond, Jean Louis

AU - Kluve-Beckerman, Barbara

AU - Benson, Merrill D.

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N2 - Background. More than 80 transthyretin (TTR) mutations have been described, most associated with amyloidosis. Peripheral neuropathy is the most common clinical presentation in TTR amyloidosis although the carpal tunnel syndrome (CTS) may be the first symptom and skin can be involved, as transthyretin amyloidosis is a systemic disease. Case report. The 78 year-old proband, belonging to a French family of Italian origin, presented with a 5 year history of peripheral neuropathy in the lower extremities. However, 15 years earlier he had had surgery for bilateral CTS. Amyloidosis was diagnosed on salivary gland and skin biopsies. Immunohistochemistry on skin biopsy was positive using anti-TTR. The proband has 10 siblings, 5 have CTS. Methods. SSCP and direct sequencing of exons 2, 3, and 4 of the TTR gene were done on DNA from the proband and his brother who had had CTS. To confirm the mutation a PCR-IMRA was done. Results. SSCP analysis of TTR exons 2, 3, and 4 did not suggest a mutation. Sequence analysis of TTR exon 3 revealed heterozygosity m both subjects for a single base-pair transversion from A to T in codon 78 (TAC→TTC) indicating a tyrosine to phenylalanine change. The mutation was confirmed by PCR-IMRA. Conclusion. This TTR mutation (Tyr78Phe) is associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. It is also associated with late onset of the disease.

AB - Background. More than 80 transthyretin (TTR) mutations have been described, most associated with amyloidosis. Peripheral neuropathy is the most common clinical presentation in TTR amyloidosis although the carpal tunnel syndrome (CTS) may be the first symptom and skin can be involved, as transthyretin amyloidosis is a systemic disease. Case report. The 78 year-old proband, belonging to a French family of Italian origin, presented with a 5 year history of peripheral neuropathy in the lower extremities. However, 15 years earlier he had had surgery for bilateral CTS. Amyloidosis was diagnosed on salivary gland and skin biopsies. Immunohistochemistry on skin biopsy was positive using anti-TTR. The proband has 10 siblings, 5 have CTS. Methods. SSCP and direct sequencing of exons 2, 3, and 4 of the TTR gene were done on DNA from the proband and his brother who had had CTS. To confirm the mutation a PCR-IMRA was done. Results. SSCP analysis of TTR exons 2, 3, and 4 did not suggest a mutation. Sequence analysis of TTR exon 3 revealed heterozygosity m both subjects for a single base-pair transversion from A to T in codon 78 (TAC→TTC) indicating a tyrosine to phenylalanine change. The mutation was confirmed by PCR-IMRA. Conclusion. This TTR mutation (Tyr78Phe) is associated with peripheral neuropathy, carpal tunnel syndrome and skin amyloidosis. It is also associated with late onset of the disease.

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KW - Skin amyloidosis

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