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Le syndrome de l'X fragile est la cause la plus frequente de retard mental hereditaire et la deuxieme cause de retard mental apres la trisomie 21. Sa frequence est de un garcon sur 4 000 et une fille sur 7 000 [9] .

Some 250 different mutations have so far been screened in the cystic fibrosis (CF) gene. The 50 nonsense, 33 splicing and 60 frameshift mutations are randomly distributed within the gene, unlike the 107 missense mutations or amino acid deletions. A large excess of missense mutations affects the exons encoding the first transmembrane (MS1) and first ATP-binding fold (NBF1) domains. Sixty-four of the 107 missense mutations may be classified as private, demic, local and general mutations on the basis of their geographic distribution in Europe. Private and demic mutations are randomly distributed within the gene; local and general mutations are not. It is well known that some RFLP markers are in linkage disequilibrium with some mutations. Private, demic and local mutations are randomly associated with each class of RFLP haplotypes. In contrast, general mutations, frequent and infrequent, are not randomly associated with RFLP markers. General mutations usually affect a specific part of the gene and are more likely to be associated with a specific RFLP marker. This suggests the existence of selective factors favoring these mutations, a hypothesis formerly postulated as a possible cause of the high frequency of the disease.

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 electrophoresis 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.

The fragile X syndrome is the most common inherited form of mental retardation. Its prevalence is estimated to be one in 1000-4000 males and one in 2000-6000 females, depending of the region. A large canadian population study in Quebec has shown a frequency of 1/260 carrier women. The fragile X syndrome was the first disease shown to be associated with "dynamic mutations", caused by an amplification of an unstable DNA sequence transmitted from generations to generations till a pathologic expression: mental retardation. The prevention is possible by a specific DNA analysis of patients and male and female carriers. It is possible to detect the mutation or the premutation in pregnant women and to propose a prenatal diagnosis by molecular study on chorionic villi samples or cultivated amniocytes.

In fragile X syndrome, the most common cause of inherited mental retardation, phenotypic expression has been linked to a region containing a repetitive sequence, (CGG)n, that appears to lengthen dramatically in fagile X patients and to show length variation in normal individuals. In order to investigate possible mechanisms responsible for further expansion of CGG in the normal population, we selected 31 normal unrelated X chromosomes carrying either the high-risk DX204-AC15 5 or DX196-AC 151 haplotypes, as defined by the flanking microsatellites, DXS548 and FRAXAC2. Nearly 100% of CGGs with more than 35 repeats were found on DX204-AC155 haplotypes, with a mean length significantly higher and much more variable than in normal individuals carrying other haplotypes including the high-risk haplotype DX196-AC151. These findings suggest that the transition from the normal to the abnormal range occurs by a multistep process, a primary event, such as unequal crossing-over, leading to increased size and moderate instability of the repeat, and from which DNA polymerase slippage could lead to recurrent premutations. Our results also suggest that the upper limit of the normal range is roughly 35 repeats in the fragile X gene. The 36–54 repeats range would define an intermediate allele only observed, up to now, in DX204-AC155 fragile X chromosomes.

In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragile X chromosomes. Contrary to observations made in myotonic dystrophy, fragile X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. We propose a putative scheme with six founder chromosomes from which most of the observed fragile X–linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen.

Thirty-seven pregnancies at risk for Niemann-Pick type C disease were monitored by study of cultured amniotic fluid cells (8 cases) or chorionic villus cells (29 cases) in 23 couples over the period 1984–91. An early protocol combined determination of sphingomyelinase activity with electron microscopy. The current strategy, based on the demonstration of specific abnormalities in intracellular processing of exogenous cholesterol, combines the study of the early phase (first 6 h) of LDL-induced cholesteryl ester formation and the histochemical evaluation (filipin staining after 24 h of LDL uptake) of the LDL-induced accumulation of unesterified cholesterol. Thirteen fetuses were predicted to be affected. Confirmation of the diagnosis was made by study of cholesterol processing in fetal skin fibroblast cultures and/or by demonstration of a characteristic lipid storage in fetal liver, already present at 14 w gestation. Definition of the biochemical phenotype (classical, variant, or intermediate) of the index case, with regard to cholesterol-processing abnormalities, is an absolute prerequisite to adequate genetic counseling in a given family. Prenatal diagnosis has now proved a safe procedure in the predominant (approximately 85%) group of families with the classical phenotype.

Having seen 87 cases we will now attempt to refine the management to be carried out when intra-abdominal hyperechogenic masses are found in the fetus. Before the 20th week of amenorrhoea (47 cases) amniocentesis can be used to study the digestive enzymes to determine the fetal karyotype. The normal results for intestinal enzymes makes it possible to rule out fetal cystic fibrosis. Three karyotype abnormalities were found in this series. After the 20th week (40 cases) intestinal enzymes cannot be interpreted. The diagnosis of cystic fibrosis then must rely on Delta F 508 mutation; but the absence of this mutation does not exclude cystic fibrosis. When ultrasound signs of intra-abdominal hyper-echogenicity are found the diagnosis of cystic fibrosis should not be thought of first, because in this series the majority of fetuses who had this sign were born without any malformation. Four cases of cystic fibrosis that were confirmed have been found but equally there were other serious malformations, three chromosome abnormalities, four intestinal atresias, ten unexplained intra-uterine deaths and one case of biliary duct atresia.

Correlations have been established between phenotype and karyotype in spontaneously aborted specimens. The criteria used to determine the phenotype were based on estimated developmental age and macroscopic examination of embryo and placenta, taking into account the morphological modifications due to in utero retention. The probability that a chromosomal aberration was the cause of the abortion is high when the developmental arrest occurred before 5-6 weeks and the expulsion was delayed. The frequency could be estimated at 75% when the developmental arrest was at 2-3 weeks, and 65% when the developmental stage reached 5-6 weeks. Main anatomical features are described permitting an attempt to assign the type of chromosomal anomaly by ultrasonographic examination.

The amniotic fluid activity of gamma glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP) and alcaline phosphatase (AP) and disacharidases was examined in 66 pregnancies with the risk of cystic fibrosis (CF) in the 17th-21st weeks of gestation. So far 28 pregnancies continue. The prenatal diagnosis was confirmed in all so far delivered children or aborted foetuses if the GGT activity was higher than 400 U/1 (10th percentile) or lower than 190 U/1 (3rd percentile) in the 17th-18th weeks. The results of other microvillar and ultrasound examinations were consistent with it. From 3 pregnancies with GGT activity in the range of 3-5 percentiles and abnormal activities of other microvillar enzymes, the CF was confirmed only in one aborted foetus with meconium ileus and with abnormal ultrasound examination. In other 2 pregnancies with normal ultrasound, healthy children were delivered. In 3 pregnancies with the GGT in the range of 5-10 percentiles and abnormal other microvillar enzymes, one false negative GGT and ultrasound examination was disclosed. The other 2 aborted foetuses did not exhibit the signs of CF in necropsy examinations. The meconium ileus was found in 2/4 of aborted foetuses with GGT lower than 3 percentiles, abnormal activities of other microvillar enzymes and abnormal ultrasound examination. The ultrasound examination was correct in 2/10 of pregnancies with GGT lower than 3 percentiles or abnormal activities of other microvillar enzymes. The GGT examination in 19th-21st weeks provided similarly reliable diagnostic results. The importance of fetal karyotyping and ultrasound elimination of other severe congenital anomalies is pointed out for critical interpretation of microvillar enzyme activities testing.(ABSTRACT TRUNCATED AT 250 WORDS)

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. © 1990 Springer-Verlag.

Fetal movements were examined by ultrasound in 24 pregnancies in which an abnormal karyotype was detected in fetal cells and compared to ultrasound fetal movement patterns in normal pregnancies. The main features in fetuses with chromosome anomalies observed at 18–20 weeks of gestation are the persistence of global, jerky movements with twitches usually seen at 13–14 weeks of gestation in normal fetuses. This fetal motor behaviour is inconstant in trisomy 21. In trisomy 18 the hand deformities are easily detected.

Une inversion pericentrique du chromosome 2 a ete decelee dans 4 familles non apparentees. Les points de cassures sont identiques en 2p11 et 2q13. Les accidents de la reproduction constates chez ces couples sont analyses. La pathologie du chromosome 2 interessant cette zone particuliere est discutee.

Serre J.-L., Feingold J., Gallano P., BouÉ J. and Boue A. — The Maintenance and Evolution of the Frequence of Abnormalities in Chromosomal Structures. An Application to some Abnormalities in Man. The genetic information of any organism is contained in a stock of chromosomes, the number and structure of which are characteristics peculiar to the species. Within each species, and more particularly in man, numerous abnormalities in number or in structure (chromosomal modifications) have been described. Though they often lend to serious pathological consequences, the frequency of some abnormalities is not negligible and some of them even can be transmitted to later generations. The study of the frequency of such abnormalities and its development is interesting for two reasons : first to attempt a forecast which shows the effect on public health; secondly, to construct a model which would account for the possible role of these modifications in evolution. The model described in this article includes several causes which tend to a variation in frequencies : mutation (probability of new cases), selection (differential mortality or fertility of those affected) and segregationKlistorsion (non-Mendelian segregation of the abnormalities in the progeny of the healthy carriers). The model shows clearly that determinist processes such as selection or segregation distorsion can only play a part in evolution through their association with stochastic processes such as genetic drift or founder effect., Serre J.-Lm Feingold J., Gallano P., Boue J. et Воий А. — Maintien et évolution des fréquences des anomalies de structures chromosomiques : Application à quelques anomalies étudiées chez l'homme. L'information génétique de tout organisme est contenue dans un stock de chromosomes dont le nombre et la structure sont des caractéristiques propres à l'espèce. Au sein de chaque espèce, chez l'homme notamment, on a décrit de nombreuses anomalies de nombre ou de structure (remaniements chromosomiques). Bien qu'ayant souvent des conséquences pathologiques graves, quelques anomalies présentent des fréquences non négligeables et certaines d'entre elles sont même transmissibles aux générations ultérieures. L'étude du maintien ou de l'évolution de la fréquence de telles anomalies a un double intérêt: le premier, pratique, est de tenter une prévision en matière de Santé Publique; le second, théorique, tend à dégager un modèle pour rendre compte du rôle possible de ces remaniements dans l'évolution. Le modèle défini dans cet article intègre plusieurs causes de variation de fréquence : la mutation (probabilité d'apparition de novo), la sélection (mortalité ou fécondité différentielle des porteurs d'anomalies) et la distorsion de ségrégation (ségrégation non mendélienne des anomalies dans la descendance des porteurs sains). L'un des résultats de ce modèle est de montrer clairement que les processus déterministes comme la sélection ou la distorsion de ségrégation n'ont pu jouer un rôle, dans l'évolution des espèces, qu'en étant associés aux effets de processus stochastiques comme la dérive ou l'effet fondateur., Serre J.-L., Feingold J., Gallano P., BouÉ J. et Воий А. — Frecuencia у evolution de ciertas anomalies en las estructuras cromosómicas : estudio de algunos casos en la especie humana. La information genética de todo organismo esta contenida en su dotación de cromosomas cuyo numero у estructura constituyen características propias de cada especie. En el seno de cada especie, principalmente en el caso de la especie humana, se han observado numerosas anomalias tanto en el numero como en la estructura de los cromosomas (aberraciones cromosómicas). A menudo estas aberraciones acarrean consecuencias patológicas graves, sin embargo algunas de ellas presentan frecuencias que no son despreciables e incluso pueden ser transmisibles a las generaciones siguientes. El estudio de la presencia y evolución de taies anomalias ofrece un doble interés : el primero, práctico, es el de sugerir medidas de prevision en el campo de la Salud Publica; el segundo, teórico, tiende a establecer un modelo que pudiera explicar el papel que estas modificaciones pueden tener en la evolución. En el modelo que se présenta en este articule- se integran varias causas de estas frecuencias : mutación (probabilidad de la aparición de una modification que no existe en los padres), selection (mortalidad o fecundidad diferenciál de los portadores de tales anomalias) y distorsion de la segregation (segrecación de carácter no mendeliano de las anomalias en la descendencia de los portadores sanos). Uno de los resultados de este modelo es el de mostrar claramente que los procesos deterministas como la selection о la distorsion de la segregation no han podido ejercer un papel en la evolución de las especies, sino que en la medida en que estos factores se han asociado a los efectos de procesos estocásticos, como la dériva genético el efecto fundador., Serre J.-L., Feingold J., Gallano P., Boué Joëlle, Boue A. Maintien et évolution des fréquences des anomalies de structures chromosomiques : application à quelques anomalies étudiées chez l'homme. In: Population, 38ᵉ année, n°2, 1983. pp. 283-310.

The fragile-X mental retardation syndrome, one of the most prevalent chromosome X-linked diseases (approximately equal to 1 of 2000 newborn males), is characterized by the presence in affected males and in a portion of carrier females of a fragile site at chromosomes band Xq27. We have performed a linkage analysis in 16 families between the locus for the fragile-X syndrome, FRAXQ27, and two polymorphic DNA markers that correspond to the anonymous probe St14 and to the coagulation factor IX gene F9. Our results indicate that the order of loci is centromere-F9-FRAXQ27-St14-Xqter. The estimate of the recombination fraction for the linkage F9-FRAXQ27 is 0.12 (90% confidence limits: 0.044-0.225) and 0.10 for FRAXQ27-St14 (90% confidence limits: 0.040-0.185). Recombination between St14 and F9 does not appear to be significantly different in normal and fragile-X families. The two flanking probes were used for diagnosis of the carrier state and for detection of transmission of the disease through phenotypically normal males. They should also allow first-trimester diagnosis with a reliability of about 98% in 40% of the families. Used in conjunction with the cytogenetic analysis, the segregation studies with both probes should improve the genetic counseling for the fragile-X syndrome and should be useful for the formal genetic analysis of this unique disease.

A pericentric inversion of chromosome 9 has been detected in 10 unrelated families. The break points are identical and the inversions involved the heterochromatic segment. The effects of inversion of chromosome 9 on different aspects of reproductive failure are discussed.

The analysis of DNA repair processes is described in two pregnancies at risk for xeroderma pigmentosum. In both cases, excision repair (measured by unscheduled DNA synthesis) and postreplication repair were analyzed. An affected and an unaffected fetus were identified within 3 weeks after amniocentesis. The cells from the affected fetus were found to be deficient in excision DNA repair, whereas the PRR patterns were intermediate between those of normal and PRR deficient cells. This indicates the possibility of prenatal diagnosis of PRR deficient XP patients (XP variants).

Associations of the three n degrees 18 chromosomes were studied in a trisomy 18 fetus (the chromosomal constitution of which had been identified by amniocentesis). The three classes of associations observed were those observed in other trisomic organisms:trivalent, trivalent presenting an important asynaptic region, and bivalent accompanied by a univalent. In addition, the sequence was established of chromomeres, the number of which varied from 18 to 23 depending on the degree of chromosome contraction. In elongated pachytene oocyte bivalents each G-band of mitotic metaphase chromosomes could be subdivided into several sub-bands.

Antenatal diagnosis enables certain fetal abnormalities to be detected "in utero", and in particular mongolism. This examination is often undertaken in the process of medical attention in pregnancy. This explains why interviews with pregnant women about this far from ordinary act have become so superficial. Men and women react differently to this take-over. The former take part in a scientific discussion, the latter, who are more closely involved, which is to say with their whole bodies, set themselves against both good and bad doctors and often try to resist this test. We have attempted to understand the meaning of wanting to or not wanting to know the sex of the child in this context before its birth, and what happens to the wish to have a child after this kind of medical care.

Twenty-eight HLA-A and B markers have been tested in 49 couples who had one or more triploid abortions. The antigen frequencies were compared to those of 209 couples and 591 normal individuals as controls. No significant deviations were observed. However, a non significant excess of antigens shared in common by both parents was shown in comparison with the normal couples. This could be related to a possible dispermy mechanism. On the other hand, a slight excess of A 28 may be in relation to a possible anomaly of gametogenesis.

Chorionic villi biopsy allows first trimester prenatal diagnosis of some genetic diseases. In this study the results of 163 diagnoses are presented, and among these, 59 diagnoses of autosomal recessive metabolic diseases with 8 observations of congenital adrenal hyperplasia due to 21 OH deficiency and 6 observations of Fanconi anemia.

Cholinesterase electrophoresis was performed in 802 amniotic fluids and its value in the detection of neural tube defects was compared with those of ultrasonography and amniotic fluid alpha-foetoprotein levels. Cholinesterase electrophoresis confirmed the ultrasonic diagnosis in 51 cases of neural tube abnormality and made it possible to diagnose neural tube defect in 6 other cases which had remained undetected by ultrasound and by alpha-foetoprotein level measurements. When our technique is used before the 28th week of gestation, false-positive results concern abnormalities which are easily detected by ultrasound (omphalocele, Bonnevie-Ullrich syndrome, sacrococcygeal tumour). We did not observe any false-negative result.

Determination of HLA antigens can be used for prenatal diagnosis of some congenital anomalies such as adrenal hyperplasia (21-hydroxylase deficiency). This necessitates rigourous HLA typing of fetal cells cultivated in vitro. The method we have developed utilizes microcytotoxicity and quantitative microabsorption tests which have been adapted to the types of cells found in these cultures.

Banding technique were applied to cell lines which had been established earlier from spontaneous human abortions and preserved frozen. Most of the autosomes were shown to be involved in lethal trisomies. As a result of the precise identification of affected chromosomes, the exact time of developmental arrest as well as certain phenotypes could be correlated with the various trisomies.

Some multisystemic abnormalities associations which can be found by ultrasound examination are sometimes chromosome anomalies and amniocentesis must be performed for confirmation. By ultrasonography we can now reach a new objective element: the fetus extremities. Limbs anomalies, such as polydactily, club-feet and/or club-hands must lead to perform amniocentesis in order to assess or not a possible 13 or 18 trisomy.

Various cytogenetic studies of early spontaneous abortions have observed trisomy 21 in about 3% of the abortuses. Analyses of prenatal diagnosis performed during the 17th week of gestation and observations on late spontaneous abortions and perinatal deaths have also shown the importance of lethal trisomy 21 in the second half of pregnancy. From these studies, it can be estimated that at least four-fifths of conceptuses with trisomy 21 fail to survive. One important question is why the same chromosome anomaly in a zygote can lead either to an early arrest of development or to a liveborn infant. Pathologic examinations of spontaneously aborted embryos with trisomy 21 have rarely shown malformations that can explain the death of the embryo, but macroscopic and microscopic examinations of their placentas show growth retardation and hypoplasia. Analysis of in vitro growth characteristics of cell lines established from tissues of trisomy 21 embryos have demonstrated differences in cell population doubling times; this may explain variations in the developmental potentials of conceptuses with trisomy 21.

Interferon sensitivity of different normal and aneusomic human cells and of different mouse-human hybrids cells has been compared. G21 trisomic cells are more sensitive than diploid cells; whereas, on the contrary, triploid cells are normal in their human interferon sensitivity. Among other aneusomic cell lines tested, E16 trisomic cells are significantly less sensitive. These data are in favor of the hypotheses that the G21 chromosome carries genetic information for structural proteins involved in the receptor system for interferon, that there is a regulatory mechanism governing the antiviral state, and that the E16 chromosome is a possible candidate for carrying information for such a depressive regulatory mechanism. None of the chromosome abnormalities studies are involved with interferon synthesis.

In diagnosing and preventing the birth of abnormal children the authors stress the necessity of team work of different specialists and their centralisation at the University complex or hospitals. The results of such a team work organised at the Division of Medical Genetics, Department of Gynecology and Obstetrics in Ljubljana and their experience in detecting some of monogenic, chromosome, and etiologically unknown disorders are presented, as well as the results of the follow-up of certain cases. The value of team work in genetic counselling is also pointed out.

Genetic, clinic and biologic features from three families with Xq fra syndrome are described. First, the authors give their experience for the best ways of culture in order to see the fragile site. Then, they insist upon the main points of each family: in the first, two women have a mental retardation; in the second, a prenatal diagnosis could be made; in the third, treatment with folic acid did not change the IQ but improves the behaviour of two brothers.

Chorionic biopsies obtained at 6–12 weeks of gestation represent a new approach in prenatal diagnosis which enables a decision on whether to terminate a pregnancy for genetic reasons to be made by the 10th–12th week of pregnancy (Kazy et al. 1982; Kaplan et al. 1983). This method has been employed for the early prenatal determination of fetal sex (Gosden et al. 1982), diagnosis of chromosome abnormalities (Brambati and Simoni 1983), fetal DNA analysis (Kaplan et al. 1983; Gosden et al. 1982; Elles et al. 1983; Old et al. 1982; Goossens et al. 1983), and the diagnosis of enzyme defects (Kazy et al. 1982; Pergament et al. 1983; Tsvetkova et al. 1983; Poenaru et al. 1984 a).

Four unexpected karyotypes were found in prenatal diagnosis: 47,XXX; 47,XXY; double reciprocal translocation; Yq-. Supplementary biological studies (including specific Y-DNA probes) are carried out in order to help in the parents' decision. No induced abortion was performed. The children are described after delivery.

Children with trisomy 21 are only a part of conceptuses with this anomaly which leads mainly to early arrests of development. Growth retardation of embryo and placenta are the main characteristics of these abortuses. Cell lines were established from tissues of trisomics 21 of different types of evolution (early spontaneous abortions, abortions after prenatal diagnosis, stillbirths and newborn-infants). Differences in the in vitro growth characteristics of these cells have been evidenced. They may explain the variations in the developmental potentials of trisomy 21 conceptuses.

The close genetic linkage between 21 hydroxylase deficiency and HLA loci considerably enlarges the possibilities of genetic counselling. Two 21-OH deficient complex families are reported, illustrating several aspects of this genetic counselling: detection of carriers, determination of the actual risk to related couples, suspicion of 21-OH deficiency by an HLA specificity association, and prenatal diagnosis.

The request for prenatal diagnosis of cystic fibrosis has been evaluated by an interview during a visit at a cystic fibrosis clinic among 32 couples whose one or several children are affected. Six couples resorted to the procedure between June 1984 and October 1985. In all the cases, in these families the only child (or children) alive was affected. The diagnosis of the disease in the first affected child reduces the number of children planned by the family. The significant use of the test, since its availability points to the existence of a real demand from the parents.

In cases of artificial insemination for genetic indication, it may be useful to determine that in fact the foetus is the result of AID. Chromosome markers may or may not provide an answer, when HLA typing of amniotic fluid cells can.

We have monitored 3 pregnancies at risk for galactosemia by deficiency in Galactose-1-Phospho uridyl transferase. Galactosemia was diagnosed in the 1st case; heterozygoty in the 2nd, and a "double heterozygoty" in the 3rd. The latter is the first example of such a diagnosis. Post natal confirmation was obtained in the three cases. Arguments are given for the usefulness of this prenatal diagnosis.