Direct diagnosis by DNA analysis is now an efficient and reliable primary test for the diagnosis of the fragile X syndrome after birth, as well as for prenatal diagnosis and genetic counseling.

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X-linked mental retardation is a very common condition that affects approximately 1 in 600 males. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Recently, a study using the candidate gene approach demonstrated the presence of mutations in PAK3 (p21-activating kinase) associated with nonspecific mental retardation. PAK3 is a member of the larger family of PAK genes. PAK proteins have been implicated as critical downstream effectors that link Rho-GTPases to the actin cytoskeleton and to MAP kinase cascades, including the c-Jun amino-terminal kinase (JNK) and p38. We screened 12 MRX pedigrees that map to a large region overlying Xq21-q24. Mutation screening of the whole coding region of the PAK3 gene was performed by using a combination of denaturing gradient gel electro-phoresis and direct sequencing. We have identified a novel missense mutation in exon 2 of PAK3 gene (R67C) in MRX47. This confirms the involvement of PAK3 in MRX following the report of a nonsense mutation recently reported in MRX30. In the MRX47 family, all affected males show moderate to severe mental retardation. No seizures, statural growth deficiency, or minor facial or other abnormal physical features were observed. This mutation R67C is located in a conserved polybasic domain (AA 66-68) of the protein that is predicted to play a major role in the GTPases binding and stimulation of Pak activity. Am. J. Med. Genet. 93:294-298, 2000.

The prenatal diagnosis of cystic fibrosis is now routinely performed by using two probes tightly linked to the CF locus (XV2C and KM19). These probes have been shown to exhibit a strong linkage disequilibrium with the CF locus. Our data (103 families) have been pooled with other French data (237 families). They are consistent with the hypothesis of a unique ancestral mutation initially associated with a B (D1E2) restriction fragment length polymorphism (RFLP) haplotype, subsequently reassociated by cross-over with A, C or D haplotypes. Assuming such an hypothesis, the mutation is supposed to be 3000-6000 years old, depending on generation length and the true recombination ratio between the KM19 and CF loci. Up-to-date Spanish, Danish and Greek data are reported together with other previously published population data in order to discuss the geographic origin and age of the mutation in Europe. The action of selection in terms of heterozygote advantage and distorsion of segregation is discussed.

Epidemiologic studies, retrospective and prospective, were done on 1500 abortions collected from 1966-1972. No secular or seasonal variations were observed. From the analysis of the relative frequencies of the different types of chromsome anomalies it is estimated that 1 out of every 2 conceptions has a chromosome anomaly. Maternal-age influence was found only for the autosomal trisomy group, mainly D and G trisomies. No effect of oral contraceptives were discovered. An increased frequency of chromosome anomalies occurred after ovulation-inducing therapy and after occupational exposure of the father to irradiation. No variations in the fertility rate and in the frequency of congenital malformations in births following abortions was noted. The incidence of recurring abortion was mainly influenced by the reproductive history of the couple before the karyotyped abortion.

No abstract

Epidemiologic studies, retrospective and prospective, were done on 1500 abortions collected from 19661972. No secular or seasonal variations were observed. From the analysis of the relative frequencies of the different types of chromosome anomalies it is estimated that 1 out of every 2 conceptions has a chromosome anomaly. Maternal-age influence was found only for the autosomal trisomy group, mainly D and G trisomies. No effect of oral contraceptives was discovered. An increased frequency of chromosome anomalies occurred after ovulation-inducing therapy and after occupational exposure of the father to irradiation. No variations in the fertility rate and in the frequency of congenital malformations in births following abortions was noted. The incidence of recurring abortion was mainly influenced by the reproductive history of the couple before the karyotyped abortion. Retrospective studyAt the time of the abortion (before the karyotype of the abortus was known) a questionnaire was completed by the parents. This questionnaire contains numerous questions concerning the medical histories of each parent, the gynecologic and obstetric history of the mother, and if feasible the circumstances surrounding conception (temperature curves, date of ovulation, dates of intercourse). Prospective studyTwo prospective studies were carried out: one in May 1971, the results of which have been published (Boue et al., '73), and a second in October 1972, in which a

A systematic study of microvillar enzyme activities in the amniotic fluid in correlation with their values in different fetal tissues during development has been undertaken. Microvillar enzymes appeared in the amniotic fluid at the time of disappearance of the anal membrane, 12-13 weeks, and declined from the 18th week until the 24th week. The study of fetal tissues and fluids has shown that gamma-glutamyltranspeptidase is mainly of liver origin. The significant decrease of the activities of these amniotic fluid enzymes has been the basis of prenatal diagnosis of cystic fibrosis. These assays may be useful for the diagnosis of certain digestive tract abnormalities at later stages of pregnancy.