On the mutation rate of neurofibromatosis

Abstract

A genetic study of 124 cases of neurofibromatosis was performed. The contingent of probands was mainly represented by a Russian population, most of the individuals being born in the European part of the RSFSR. Both parents of the probands were examined in only 58 cases, the proportion of sporadic cases in this group being 0.79, as compared to 0.77 for the whole group under study. The existing data evaluated by a direct method are not yet sufficient for a decisive estimation of the penetrance, which, however, cannot be under 80%. Segregation analysis of descendants from particular marriages showed a good correspondance to the hypothesis of Mendelian dominance (32 affected children out of 65). These results analyzed together with those obtained by other authors permit an inference on the full penetrance of neurofibromatosis. The genetic interpretation of sporadic cases as a result of new mutations is presented. The prevalence of neurofibromatosis among the 16-year-old youths was evaluated as 12.8 with 10-(5). This value is suggested to be an estimation of the incidence of the condition in the general population, the mutation rate evaluated by a direct method being equal to 4.4 with 10-(5) divided by 4.9 with 10-minus 5. The increased birth order of probands in sporadic cases (against the theoretical expectation) as well as increased paternal age (as compared with controls) were found to be statistically significant (P equals 0.004 and P equals 0.03, respectively) while the difference in maternal ages was statistically insignificant (P equals 0.008). No statistical relationship between sporadic cases and occupational exposure of parents to deleterious chemical and physical factors was found.

Epidemiology of neurofibromatosis type 1

“…Clementi et al [1990] observed a higher prevalence of NF1 among children under 9 years of age, a group that was excluded from the studies of Sergeyev [1975] and Samuelsson and colleagues [Samuelsson and Axelsson, 1981;]. Huson andassociates [1988, 1989a] also found a higher prevalence of NF1 among younger individuals.…”

“…No cases of nonpenetrance were observed in thorough clinical studies of some 200 multigeneration families [Crowe et al, 1956;Sergeyev, 1975;Riccardi and Lewis, 1988;Huson et al, 1989a;Samuelsson and Akesson, 1989;. Although anecdotal instances of nonpenetrance have been reported [Carey et al, 1979;Spence et al, 1983], no case has been documented with mutation analysis or linkage and full clinical evaluation using the NIH diagnostic criteria.…”

“…The studies upon which these estimates are based are summarized in Table 1. The lowest reported prevalence is from a study of healthy army recruits [Sergeyev, 1975], a group that might be expected to exclude all severely affected NF1 patients. Some NF1 patients were probably missed in the other populations studied because mildly affected individuals do not come to medical attention [Huson et al, 1989a;Clementi et al, 1990].…”

Prevalence of Neurofibromatosis 1 in German Children at Elementary School Enrollment

“…6-8 EstimatesoftheprevalenceofNF1 have ranged from 1.0 to 10.4 per 10000 in various populations, [9][10][11][12][13][14][15][16][17] but the prevalence has not been studied in Germany.…”

Estudo molecular do gene TCOF1 em pacientes portadores da síndrome de Treacher Collins

“…A incidência estimada da STC é de 1/50.000 nascimentos, com 60% dos casos resultantes de mutações novas (Jones, 1997). Depois de rever 98 casos descritos na literatura, Jones et al (1975), sugeriram que os casos esporádicos da STC estavam associados a um aumento da idade paterna, o que já havia sido sugerido para outras síndromes de herança autossômica dominante, como acondroplasia (OMIM 100800), síndrome de Marfan (OMIM 154700), síndrome de Apert (OMIM 101200) e neurofibromatose tipo I (OMIM 162200), entre outras (Penrose, 1957;Murdoch et al, 1972;Erickson & Cohen, 1974;Sergeyev, 1975).…”