The genetic studies of familial amyloid polyneuropathy in the Arao district of Japan: II. Studies of genetic markers in blood

Abstract

SummaryBlood samples from 21 patients with familial amyloid polyneuropathy (FAP) and 81 normal family members among 7 affected families in Arao were tested for 9 blood group systems, 8 serum polymorphic proteins, 12 red cell polymorphic enzymes, and HLA. One of the most important findings was the existence of two relatively rare variants, i.e., group specific component Gc*IA2 and phosphoglucomutase PGMI*7 in 3 families. This observation suggests that the three genealogically independent families may have a common ancester. Phenotype AB in the ABO blood group system, phenotype 1 in the haptoglobin system, and M2 gene in the protease inhibitor system were not seen, and phenotype Jk(a+b-) in the Kidd groups was found in only one patient. Whether these observations reflect the characteristics of FAP in the Arao district or that of FAP itself can not be determined from the present study. No phenotype attributable to Caucasians was found, hence the study provides no support for the hypothesis that the gene for FAP was introduced into Japan by the Portuguese.

Genetic studies of familial amyloid polyneuropathy in the Arao district of Japan

“…The finding that the structural abnormality (prealbumin 30 Val ~ Met) was identical, irrespective of the subject or the family is particularly valuable from two genetic aspects, First, it supports our view that the families afflicted with FAP in Arao may have a common ancestor (Sakoda et al, 1984), although there are nine genealogically independent families (Sakoda et al, 1983). If we combine the findings presented in this report with information on the distribution of two rare variants, i.e.…”

“…If we combine the findings presented in this report with information on the distribution of two rare variants, i.e. phosphogluc0mutase 7 and group specific component J (Sakoda et al, 1984), we can conclude that five of the nine families have a common ancestor. Whether or not 'the FAP gene in the Arao focuS is derived from the Protuguese reamins an interesting enigma (Andrade et al, 1970): Second, it lends credence to the view that the prealbumin variant is essentially concerned with the pathogenic mechanism of this gerteticatly determined neuropathic disease.…”

“…Case t, T.H., a 47-year-old man, is a member of the U family; case 2, T.Y., a 41-year-old woman, is a member of the S family; case 3, O.M., a 51-year-old man, is a member of the H family; and case 4, T.M., a 46-year-old woman, is a sister of case 3. The U, S and H families are genealogically independent of one another (Sakoda et al, 1983). Each patient had a typical clinical course of FAP and the diagnosis made by clinical features and family history was confirmed by autopsy.…”

“…(1968), affects nearly one hundred patients among nine families (Sakoda et al, 1983). Subsequent studies of genetic markers in blood suggested that 3 of 7 families examined in Arao have a common ancestor (Sakoda et at., 1984).…”

Onset in the seventh decade and lack of symptoms in heterozygotes for the TTRMet30 mutation in hereditary amyloid neuropathy—type I (Portuguese, Andrade)

“…Overall penetrance, using Morton's method for late onset diseases, and discarding sibs below age 20, was calculated at 83.5% by Sakoda et al [1983]; in two families, whose pedigrees are shown, there are several instances of skipped generations, though age at death of the unaffected heterozygotes is not provided.…”