Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.

Familial amyloidosis, Finnish type (FAF), is an autosomal dominant form of familial amyloid polyneuropathy. The novel amyloid fibril protein found in these patients is a degradation fragment of gelsolin, an actin-binding protein. We found a mutation (adenine for guanine) at nucleotide 654 of the gelsolin gene in genomic DNA isolated from five FAF patients. This site is polymorphic since the normal allele was also present in all the patients tested. This mutation was not found in two unaffected family members and 11 normal controls. The A for G transition causes an amino acid substitution (asparagine for aspartic acid) that was found at position 15 of the amyloid protein. The mutation and consequent amino acid substitution may lead to the development of FAF.

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“…8) and two unaffected family members of FAF patients (nos. 6 and 7) . Genomic DNA sequences 565-680 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Levy

Haltia

Fernandez-Madrid

et al. 1990

The Journal of Experimental Medicine

142

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“…2 Progression is typically slow over several decades. 12 Dysphagia and dysarthria due to bulbar palsy may occur.…”

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confidence: 99%

Gelsolin‐related familial amyloidosis, Finnish type, in a Portuguese family: Clinical and neurophysiological studies

et al. 2003

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We report a Portuguese family with familial amyloid polyneuropathy related to gelsolin. There were no known Finnish ancestors, but the same mutation as described in Finnish patients (G654A) was carried. Clinical and neurophysiological investigations were performed in four patients. Corneal lattice dystrophy affected all four patients; an axonal lesion of the facial nerve occurred in three patients; visual tract involvement was documented in one case; and corticospinal and posterior column dysfunction was present in one patient. Polarizing microscopy of skin and muscle samples demonstrated amyloid deposits in two patients; anti-gelsolin immunohistochemistry was positive for amyloidogenic gelsolin. The Finnish mutation of gelsolin protein (G654A) was detected in five family members. The utility of neurophysiological testing in the evaluation and follow-up of this type of amyloidosis is discussed.

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“…The disease is, however, not limited to Finland. Cases have also been described from the United States (4)(5)(6), Denmark (7), and the Netherlands (8).…”

Section: Introductionmentioning

confidence: 99%

Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin.

Maury¹

1991

J. Clin. Invest.

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The Finnish type of familial amyloidosis is a systemic disease characterized by progressive cranial neuropathy, corneal lattice dystrophy, and distal sensimotor neuropathy. Amyloid fibrils were isolated from the kidney and heart of a patient with Finnish amyloidosis. After solubilization, the amyloid proteins were fractionated by gel filtration and purified by reverse-phase HPLC. Complete amino acid sequence analyses show that the two amyloid components obtained are fragments of gelsolin, an actin-modulating protein occurring in plasma and the cytoskeleton. The larger component represents residues 173-243 and the minor component residues 173-225, respectively, of mature gelsolin. When compared with the predicted primary structure of human gelsolin a single amino acid substitution is present in amyloid: at position 15 of the amyloid proteins an asparagine is found instead of an aspartic acid residue at the corresponding position (187)

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Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.

Cited by 72 publications

References 18 publications

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Mutation in gelsolin gene in Finnish hereditary amyloidosis.

Gelsolin‐related familial amyloidosis, Finnish type, in a Portuguese family: Clinical and neurophysiological studies

Gelsolin-related amyloidosis. Identification of the amyloid protein in Finnish hereditary amyloidosis as a fragment of variant gelsolin.

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