TY - JOUR
T1 - Familial amyloidosis, Finnish type
T2 - G654 → A mutation of the gelsolin gene in Finnish families and an unrelated American family
AU - de la Chapelle, A.
AU - Kere, J.
AU - Sack, G. H.
AU - Tolvanen, R.
AU - Maury, C. P.J.
N1 - Funding Information:
This work was supported by grants dation and the Academy of Finland. at the Folkhlilsan Institute of Genetics. can patient were prepared by the Center (MD 24061).
PY - 1992/7
Y1 - 1992/7
N2 - The Finnish type of familial amyloid polyneuropathy (FAF) is an autosomal dominant form of systemic amyloidosis caused by a mutation in the gelsolin gene. The mutation leads to the expression of amyloidogenic mutant Asp187 → Asn gelsolin, an actin-modulating protein. We previously developed a DNA test based on amplification by the polymerase chain reaction followed by allele-specific oligonucleotide hybridization that identifies the base substitution adenine for guanine at nucleotide 654 in the gelsolin gene causing the disease. We show here that the same mutation is present in members of six apparently unrelated Finnish families and in a member of an unrelated American family. These results, taken together with previously published findings in nine additional Finnish families and another unrelated American family, indicate that most, perhaps all, FAF patients in Finland and possibly worldwide carry the same mutation. We suggest two alternative explanations: (i) the mutation arose in a very early common ancestor or (ii) the Asn187 mutation is particularly, perhaps uniquely, amyloidogenic.
AB - The Finnish type of familial amyloid polyneuropathy (FAF) is an autosomal dominant form of systemic amyloidosis caused by a mutation in the gelsolin gene. The mutation leads to the expression of amyloidogenic mutant Asp187 → Asn gelsolin, an actin-modulating protein. We previously developed a DNA test based on amplification by the polymerase chain reaction followed by allele-specific oligonucleotide hybridization that identifies the base substitution adenine for guanine at nucleotide 654 in the gelsolin gene causing the disease. We show here that the same mutation is present in members of six apparently unrelated Finnish families and in a member of an unrelated American family. These results, taken together with previously published findings in nine additional Finnish families and another unrelated American family, indicate that most, perhaps all, FAF patients in Finland and possibly worldwide carry the same mutation. We suggest two alternative explanations: (i) the mutation arose in a very early common ancestor or (ii) the Asn187 mutation is particularly, perhaps uniquely, amyloidogenic.
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U2 - 10.1016/0888-7543(92)90182-R
DO - 10.1016/0888-7543(92)90182-R
M3 - Article
C2 - 1322359
AN - SCOPUS:0026764358
SN - 0888-7543
VL - 13
SP - 898
EP - 901
JO - Genomics
JF - Genomics
IS - 3
ER -