The polymerase chain reaction is a new powerful method for in vitro cloning of specific regions of DNA. The use of the heat-stable DNA polymerase made the reaction amenable to automation. This method greatly facilitates the detection of mutations which are responsible for Duchenne muscular dystrophy, via DNA amplification of multiple deletions prone exons from the DMD gene.
R.F.L.P. (Restriction Fragment Length Polymorphism) observed with tightly linked probes to the CF gene allows us to calculate the standardised linkage disequilibrium between CF and these markers. This approach in combination with others strategies permits to situate the gene between D9 and G2. The conditional probabilities observed with these haplotypes modify the classical genetic of CF.
: We report a case of mental retardation associated with multiple congenital anomalies suggesting an F.G. syndrome. We discuss problems concerning genetic counselling and the management of future pregnancies. Unfortunately, no concrete strategy, concerning prenatal diagnosis, can be proposed.
Two brothers are described with a severe syndrome of postnatal growth and mental retardation which includes extreme microcephaly, obesity developing during infancy, microgonadismsm, and a characteristic amphora-shaped facies. The neurological exam is highly abnormal, with hypertonia and hyperreflexia, nystagmus, and an extremely irritable and agitated behavior. The first child, who died at 4/1/2 years, also presented neonatal hypoglycemia and chronic constipation. Although the etiology of this syndrome is unknown, it is tempting to consider an X-linked recessive gene, given the importance of the X chromosome in mental retardation. Among the over 70 syndromes of X-linked mental retardation already described, our patients resemble individuals with the Börjeson-Forssman-Lehmann (BFL) syndrome the most. However, the severity of their dwarfism and mental retardation is much greater than described in any BFL patient to date, and the neurological and dysmorphic features vary significantly from those described in the BFL. Although a particularly severe variant, perhaps allelic, is a possibility, an as yet undescribed disorder is also plausible, the etiology of which would probably be recessive, either autosomal or X-linked.
The authors report the case of a newborn full term delivered by cesarean section for evolutive hydrocephalus, in the last month of pregnancy. This hydrocephalus was confirmed by echography after birth. This also having ambiguous genitalia and atresia ani, he died a few hours later. No evidence of infectious or toxic embryofetopathy was found out as an etiologic factor, but the karyotype of the baby showed a 13 q deletion and that of the mother a non reciprocal Xqter; 13q31.3 translocation. The study of inactivation of X indicated that the inactivated X chromosome in each cell was normal. On this occasion, the authors try to bring together the main points of "13q-syndrome" and discuss on the practical approach of antenatal diagnosis which they could propose to the couple.
Cystic fibrosis (CF) is always a common lethal genetic disease. The locus is localized to human chromosome 7q22-7q31. Genetic linkage between the CF locus and polymorphic DNA marker is used to realize family studies. We have genotyped 56 families (352 patients) with a CF child. The informativeness with the six markers (Met D/Taq I, Met H/Taq I, Met H/Msp 1, XV2c/Taq 1, km19/pst pJ 3.11/Msp 1) is important (96%). The linkage desequilibrium between alleles detected by XV2 c and Km 19 described by Estivill and al, is also showed in our population. The haplotype B (Km 19 = 6.6 kb, XV2 c = 2.1 kb) is present on 84% of our 112 CF chromosomes. We have established the frequencies of the 10 possible genotypes in the pool of the 112 CF chromosomes and in the pool of the normal chromosome and according to Bayes obtained the predictive positive value to be heterozygote. It is possible to precise the genetic counselling in these families.
Five hundred children and adolescents affected by mild mental retardation were studied together with their families with regard to a number of psycho-social, medical and genetic factors. Statistical studies were performed with these data and showed that this apparently homogeneous population could in fact be divided into three subgroups. The first and by far the largest group (66%) was constituted by a clinically normal population but in whom adverse social and cultural factors were dominant. In the second subgroup (20%) the mental retardation was much more pronounced (IQ of 50----65) and the socio-cultural and socio-economic levels were particularly low. Finally, organic causes (prematurity, dystocic, labour, etc.) seemed to constitute the principal factor explaining the retardation observed in the third subgroup (14%). The second subgroup comprising of 50 children and their families, were observed more closely; in this group 20 cases of known genetic diseases were found.
We report linkage studies between Emery-Dreifuss muscular dystrophy (EDMD) and polymorphic probes from the long arm of chromosome X in two pedigrees. The results don't show significant linkage but are consistent with previous localisation of EDMD in Xq28. Further studies will be necessary to apply molecular biology to genetic counselling and prenatal diagnosis of this disease.
A dialogue between a geneticist and a M.D. trained in medical psychology has been established about problems arising in genetic counselling. A better knowledge of themselves allows them to increase the quality of genetic counselling by improving the communication techniques. The whole personality and not only the genetic disease of the individuals seeking genetic counselling is taken into account during the counselling process.
The increased availability of recombined human growth hormone (rhGH) allows its possible use in clinical situations not classically recognized as regular indications. Among these, the Turner's short stature is presently under experimental evaluation for its responsiveness to rhGH. Twelve patients, 10 with a 45, X karyotype, 1 46 XXiq, and 1 mosaicism, have been given rhGH at a dosage of 0.15 U/kg per injection six times a week. Mean age at onset of treatment was 12.8, mean growth retardation was 4.1 SDS according to Sempé. After 18 months of treatment mean growth catch-up was 0.9 SDS. Maximal velocity was reach during the first trimester of treatment and decreased thereafter but was above normal for bone age in all but 2 after 18 months. The bone age increased less than structural age. No side effects were reported. At the present time the efficacy of rhGH in increasing final height in Turner's patients is likely but not demonstrated by any studies. The exact place of ovarian substitution, even during the prepubertal period, is still matter of discussion. Since the velocity response to rhGH was maximal among the youngest patients an early diagnosis of the syndrome will likely be necessary to improve final stature.
Clinical and cytogenetic studies are performed on 14 patients with PWS including endocrinological investigations, as coagulation factor XI activity and pigmentation studies. Recent hypothesis from molecular analysis are discussed.
The case of a 4 years old boy, hospitalized for an unexplained coma, is reported. He is the first child of a non-consanguin couple. The psychomotor development of this child was considered as normal up to the age of 18 months; then, a delay in language development, behaviour disorders with an important instability interrupted by episodes of somnolence, were observed. This child was treated for psychotic disorders. At the age of 3 and half, he had two episodes of seizures associated with fever. He was hospitalized for a 24 hours coma (4 years old). An hepatomegaly and a dry, brittle hair were then observed. Hyperammonemia was made obvious by a protein tolerance test. The diagnosis of argininosuccinate lyase (ASAL) deficiency was based on the increased levels of ASA in plasma and urine. The deficiency was proved by a fibroblast culture. With protein restriction, hepatomegaly disappeared, hair became normal, the behaviour disorders and the delay in language development was improved. However, some school difficulties persist. This case shows that an hereditary metabolic syndrome can be revealed by psychotic like symptoms in childhood.
The author describes three different opportunities requiring a desirable collaboration between the geneticist and the psychiatrist: 1. More detailed analysis of the psychologic fallout inside a family with an handicapped person. 2. How a geneticist may contribute to a medical progress inside a psychiatric institution. 3. The possible convergence of their efforts in some fields of the neuropsychiatric research.
As of December 1, 1988, we had, as part of our prenatal diagnostic service, studied 458 transcervical chorionic villus biopsies. Three-fourths of these samples were taken because of advanced maternal age (greater than or equal to 35 years), whereas nearly one fifth were done to alleviate parental anxiety. The remainder were performed because of a precedent chromosomal anomaly in child or parent, to determine fetal sex in the case of X-linked familial disorders, or to obtain DNA for molecular analyses. Among the cytogenetic anomalies detected after 24 to 48 hours of culture, eight involved classical trisomies. In four other instances the chromosomal abnormalities were more difficult to interpret (mosaic trisomies 10, 13 and 15, an apparently uniform trisomy 7). All four were revealed to be "false positives", since neither the amniocenteses nor the karyotypes of the normal newborns (one pregnancy is still ongoing) confirmed an abnormal karyotype. In the case of the trisomy 7 we were able, after birth of the baby, to study two placental biopsies, one of which revealed an abnormality distinct from that detected in the chorionic villi. The observations concerning a fifth false positive are more worrisome, as an apparently uniform trisomy 18, with a fetus showing growth retardation on ultrasound, could not be confirmed in the abortus. Otherwise, we have not encountered a false negative result. In this article we discuss the mechanisms potentially responsible for the cytogenetic discrepancies sometimes observed between fetal and placental tissues. Molecular analyses may help to establish whether a chromosomal anomaly present in fetal chorionic villi had its origin in the pre- or post-zygotic stage; in the latter case the aneuploidy may be uniquely extrafetal.
When a children psychiatrist, faced to atypical psychological troubles, comes up against difficulties in establishing a precise diagnosis, he may consider a genetic etiology and ask for a genetic consultation. He may encounter many problems when he suggests this specialized consultation to the parents. These have often been prepared for a long time to the necessity of a psychiatric therapy in order to cure their child's troubles. The geneticist's diagnosis will induce the parents and the psychiatrist to have a different look on the child and mostly will set limits to the possibilities of treatment.
The Jarcho-Levin syndrome is an autosomal recessive disease characterized by spinal and rib malformations (spondylocostal dysplasia). The case reported concerns a fetus with a dorsal spine angulation noted at the 15th week of gestation. A more accurate ultrasound study performed at 20 weeks revealed shortness of the neck and thorax, irregular ribs and vertebrae and absence of other visceral abnormalities. The karyotype was normal. Therapeutic abortion proposed was finally accepted by both parents at 27 weeks. The diagnosis was confirmed by post mortem radiography. No parental consanguinity was noted.
