Attitudes and knowledge about presymptomatic genetic testing among individuals at high risk for familial, early-onset Alzheimer's disease.

The study was conducted in a large Cuban family with early-onset familial Alzheimer's disease (AD). Fifty-six first-degree relatives of familial cases with AD were interviewed concerning their clinical and genetic knowledge about AD and their attitudes toward the possible use of presymptomatic genetic testing of AD. The individuals had only limited knowledge about their personal risk of developing AD. All 56 family members would use presymptomatic testing to know their own risk of AD. Confronted with a hypothetical reproductive choice, 50% would choose not to have children if they themselves had the mutation. A positive prenatal test would lead 48.2% of the participants to have an abortion, and 19.7% would continue the pregnancy regardless of the positive test result.

Results of 12 years' combined maternal serum alpha-fetoprotein screening and ultrasound fetal monitoring for prenatal detection of fetal malformations in Havana City, Cuba.

Progressively since 1982 and as part of a nationwide programme for the diagnosis and prevention of genetic diseases, maternal serum alpha-fetoprotein (MS-AFP) screening and ultrasound fetal monitoring has been implemented in all pregnant women in Cuba. In Havana City, 328,983 pregnant women underwent MS-AFP screening between 15 and 19 weeks of gestational age. With a cut-off level of > or = 2 multiples of the normal median (MOM), 1767 amniocenteses were carried out to determine the levels of amniotic fluid AFP and 685 malformed fetuses were diagnosed. By ultrasound fetal monitoring, an additional 686 malformed fetuses were detected. As a result of the programme, the birth prevalence of neural tube defects has fallen by 90 per cent.

Genetic aspects of polydactyly.

The early limb development follows the similar pattern in all vertebrates since different species develop using the same regulatory genes in the formation of the body plan. Some of these genes remained well conserved during evolution and can be traced back as far as Drosophila--while some others changed their structure or developed new functions. This is why the limbs from different animals still look different from one another. However, all existing tetrapods have, like Homo Sapiens, limbs with five, or fewer digits. It has been argued that the interplay of the factors controlling the patterning and differentiation during the embryonal limb development can provide five distinct "genotypes" allowing development of only five different digits. This would imply that the Greek definition of polydactyly, namely "duplication of the finger or a part of it", is correct, not only in morphological but also in a genetical sense. Genes involved in the determination of the outline of the limb are candidates for disorders like polydactyly and syndactyly. Recently, we have localised the gene for triphalangeal thumb (TPT) on chromosome 7q. As almost 50% of our patient population also had rudimentary postaxial polydactyly and/or syndactyly, the interesting question arose whether the TPT gene also was responsible for isolated post-axial polydactyly. Our preliminary evidence suggests, however, that different gene(s) are involved in the pathomorphogenesis of postaxial polydactyly. Studies of human congenital hand malformations--combined with genetic studies in lower vertebrates--will help us to understand not only the molecular basis of these disorders, but also to get insight into the fascinating mechanisms involved in the normal development of the human hand.

Genetic mapping of the spinocerebellar ataxia 2 (SCA2) locus on chromosome 12q23-q24.1.

A refined genetic map of the spinocerebellar ataxia 2 locus was constructed through linkage and haplotype analysis of 11 large pedigrees from the Holguín SCA2 family collective. Three-point analysis makes a localization of the SCA2 mutation in the 6-cM interval D12S84-D12S79 likely. This is consistent with haplotype results indicating a crossover event between two branches of the SCA2 family Rs and placing the mutation on the telomeric side of D12S84. The microsatellite D12S105 within this interval shows a peak two-point lod score of Z = 16.14 at theta = 0.00 recombination and complete linkage disequilibrium among affected individuals. These data together with the observation of a common disease haplotype among all family ancestors support the notion of an SCA2 founder effect in Holguín province.

Frequency of delta-F508 mutation and XV2C/KM19 haplotypes in Cuban cystic fibrosis families.

We tested the frequency of the delta F508 mutation and haplotypes linked to the cystic fibrosis (CF) gene in Cuba. The delta F508 deletion was detected in 34.0% of the CF chromosomes. There was a shortage of delta F508 heterozygotes, suggesting non-randomness in mating patterns. Haplotype B (XV2C/KM19 1/2) was found on 40.5% of the CF chromosomes (71.5% of delta F508 chromosomes, 28.3% of non-delta F508 CF chromosomes) against 13.5% of non-CF chromosomes.

Results from a reference laboratory for prenatal diagnosis of sickle cell disorders in Cuba.

A nationwide programme for the prevention of sickle cell (SS and SC) disorders was initiated in Cuba in 1983. Couples at risk were identified by screening pregnant women and the partners of those who carry an abnormal haemoglobin, followed by genetic counselling and the offer of prenatal diagnosis. Prenatal diagnosis was performed in one laboratory, which had carried out 1068 prenatal tests for Hb SS and SC disorders by the end of 1992. The centralization of the service has permitted rapid identification and resolution of problems.

Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1.

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders characterized by onset with gait ataxia, dysarthria, dysmetria and dysdiadochokinesia. We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the documented spinocerebellar ataxia locus (SCA1) on chromosome 6p in a large Cuban founder population. We now report the assignment of a second locus for ADCA (SCA2) to chromosome 12q23-24.1 following linkage analyses carried out for the Cuban pedigrees, with probable flanking markers D12S58 and phospholipase A2. Investigation of linkage to the interval containing SCA2 for seven French ADCA families, previously excluded from linkage to SCA1, provides preliminary data suggesting the existence of a third ADCA locus (SCA3).

Cuban programme for prevention of sickle cell disease.

The percentage of carriers of the sickle cell gene in Cuba ranges from 3 to 7% in different regions. In 1983 the National Medical Genetics Centre initiated a programme for the control of sickle cell disease, which was started in Havana and later extended nationwide. The programme is based on mass education, screening and supportive genetic counselling, care of affected individuals, and availability of prenatal diagnosis. 806,935 pregnant women had been screened by the end of 1989: 29,913 (3.7%) were heterozygous, homozygous or doubly heterozygous for abnormal haemoglobin. 19,686 fathers (67%) were also tested: 1268 at-risk couples were detected. 531 elected to have prenatal diagnosis; 404 results were obtained and 98 affected fetuses (SS or SC) found. In 72 cases the pregnancy was terminated.

Cuban Programme for Prevention of of Sikle Cell

The percentage of carriers of the sickle cell gene in Cuba ranges from 3 to 7 percentil in different regions. In 1983 the National Medical Genetics Centre initiated a programme for the control of sickle cell disease, which was started in Havana and later extended nationwide. The programme is based on mass education, screening and supportive genetic counselling, care of affected individuals, and availability of prenatal diagnosis. 806 935 pregnant women had been screened by the end of 1989: 29 913 (3.7 percent) were heterozygous, homozygous or doubly heterozygous for abnormal haemoglobin. 19 686 fathers (67 percent were also tested: 1268 at-risk couples were detected.531 elected to have prenatal diagnosis; 404 results were obtained and 98 affected fetuses (SS or SC) found. In 72 cases the pregnancy was terminated(AU)

Maternal serum alpha-fetoprotein screening for neural tube defects and other disorders using an ultramicro-ELISA. Collaborative study in Cuba and in the German Democratic Republic.

In Cuba and in the German Democratic Republic (GDR) a total of 24,412 pregnant women were tested for maternal serum alpha-fetoprotein (MSAFP) at the 16th to 20th week of gestation. An inexpensive and partly automated ultramicroliter enzyme immunoassay (ELISA) with final volumes of 10 microliter was used to analyze simultaneously 50 samples. The intraassay coefficient of variation (CV) of 5-8% and day/day CVs of 6-10.5% were obtained with a test frequency of 320 assays/day. A cut-off level of twice the median value (MoM) was chosen. An amniocentesis was done in a total of 0.5% (in the GDR) and 0.7% (in Cuba) of the screened women. The prevalence of open neural tube defects (ONTD) was calculated from the present study and was 1.43% in Cuba and 1.34% in the GDR. Through MSAFP screening 88.2% ONTD were detected. There was no therapeutic abortion of a normal fetus. The approximate cost for this program was about 2.36 marks-GDR per patient screened, or about 2,048 marks per ONTD detected.

Haemoglobin Porto Alegre in a Cuban family.

During a screening programme for abnormal haemoglobins in Habana, one case of Hb Porto Alegre was found in 23 000 cases analysed. The ability of this variant to polymerise in vitro and the absence of clinical features in the carriers have been confirmed. These observations are now explained by the findings of high levels of glutathione in the red cells of subjects heterozygous for Hb Porto Alegre: it is suggested that the increase of glutathione is responsible for the absence of in vivo polymerisation and accounts for the lack of clinical symptoms.

A new form of the solubility test for hemoglobin S; results from a survey of 3000 cases.

A new form of the solubility test for the detection of Hemoglobin S is described. Glass ampoules containing one ml of the test solution ready for use are employed; they can be stored for more than one year at 4 degrees C. 3000 blood samples were analyzed by the solubility test and electrophoresis. The comparison between the two methods showed that the solubility test is highly satisfactory.