Infantile cystinosis in France: genetics, incidence, geographic distribution.

Abstract

Summary. A national distribution of 66 French patients, from 49 sibships, has been studied. Segregation analysis, using the maximum likelihood method, was found to agree with the theoretical values expected in recessive autosomal inheritance. The birthplaces of these patients show an unequal geographic distribution of cystinosis, the incidence being higher in Western France. Compared with the total number of live births during the period 1959 to 1972, the minimum incidence of the condition in the province of Brittany is 1 per 25 909, and the gene frequency 0.0062. In the rest of France, the minimum incidence is 1 per 326,440 and the gene frequency 0.0018. Application of Dahlberg's formula gives a similar result. The mean inbreeding coefficient is 530 x 10-5, a figure 23 times higher than the mean coefficient of France. An indirect test of inbreeding, the distance between parental birthplaces, was studied, first using the French administrative boundaries, second by using kilometres. This distance was constantly smaller for the parents of patients than for the parents of controls. Analysis of two erythrocyte polymorphisms (ABO and Rh) showed a large excess of group A patients when compared with overall French data. These findings are difficult to interpret on genetic grounds. The genetic reasons for the unequal geographic distribution of cystinosis in France are discussed.

Genotypic and phenotypic features of the cystinosis patients from the South Eastern part of Turkey

“…The most common type in our study, the c.451A>G mutation, was previously described in Turkey and associated with a moderate clinical course 16 . Similarly, all of our patients with the c.451A>G mutation (2,3,4,10,11,12,14,16,20) were diagnosed between the ages of 2 to 14 years with renal tubular acidosis (RTA), excluding only one patient. Patient 16, who was on Three out of seven patients with the c.681G>A mutation are on the CAPD program due to renal failure.…”

“…The incidence rate of nephropathic or classical infantile cystinosis is estimated to range from 1:100000 to 1:200000 in North America 2 . In West Brittany, France, the incidence rate is much higher (1:26000) compared to the rest of the country (1:320000) 3 . The indicating signs of renal involvement are dominant in that group, which is also the most frequent type with severe phenotype.…”

Etude clinique genetique et epidemiologique du syndrome de Zellweger et de la cystinose au Saguenay-Lac-St-Jean

“…En effet des 42 familles étudiées 6 étaient apparentées et le coefficient moyen de parenté des parents était de 53 x 10" 4 (Bois et al 1976). …”

“…Si l'on regarde l'incidence de la cystinose au SLSJ qui est de 1 pour 11 939 naissances on constate qu'elle est deux fois plus élevée que celle calculée en Bretagne (France) qui est de 1 pour 25 909 naissances, ce qui était considéré comme étant très élevé soit 12.5 fois plus élevée que dans le reste de la France (Bois et al 1976);…”

“…de plus l'incidence de la cystinose au SLSJ est au moins 10 fois supérieure à l'incidence mondiale qui est évaluée de 1 pour 100 000 à Le taux de porteurs pour la région est de 1 pour 55 habitants comparativement à 1 pour 77 habitants en Bretagne (Bois et al 1976), et de 1 pour 200 habitants dans la population mondiale en général (Gahl et al 1989). …”