[Distribution of dominant hereditary ataxias and Friedreich's ataxia in the Spanish population]. / Distribución de ataxias hereditarias dominantes y ataxia de Friedreich en la población española.

BACKGROUND: To establish the distribution of the different forms of dominant ataxias and Friedreich ataxia in Spanish population. PATIENTS AND METHODS: We have performed a molecular study in 121 patients presenting ataxia as the first sign of neurodegenerative disease. In these patients, we have performed a molecular study of SCA 1, SCA 2, SCA 3, SCA 6, SCA 7, SCA 8, DRPLA, alpha-TTP (tocopherol transfer protein) and Friedreich's ataxia genes. RESULTS: The study showed that the Friedreich ataxia is the most frequent form representing 34.4% of the total of the hereditary ataxias. One patient presented mutation in alpha-TTP gene. Among the dominant forms SCA 3 was the most frequent (27.3%) followed by SCA 7 (16%), SCA 6 (9%) and SCA 2 (4.5%). We have not found mutations in SCA 1 and DRPLA genes. Two of 60 apparently sporadic cases presented mutations in the SCA 6 and SCA 8. CONCLUSIONS: The genetic analysis is the principal method to distinguish the different clinic forms of ataxia. We have not found mutations in 41.2% of dominant forms and in 43.3% of recessive forms. These results suggest the existence of new candidates genes.

[Quick diagnosis of Prader-Willi and Angelman syndromes by means of methylation test by PCR]. / Diagnóstico rápido del síndrome de Prader-Willi y de Angelman mediante test de metilación por PCR.

OBJECTIVE: Angelman (AS) and Prader-Willi (PWS) syndromes are two different neurogenetic diseases caused by a deficiency of maternal (AS) or paternal (PWS) contributions of the region 15q11-13. Molecular diagnosis of these pathologies can be accomplished by several techniques: DNA polymorphism (microsatellite) analysis, cytogenetic techniques of fluorescent in situ hybridization (FISH) and methylation test by Southern blot (SB), with the latter being the most reliable. Recently, a new technique, based on the study of methylation through treatment with sodium bisulphite and subsequent polymerase chain reaction (PCR), has become available. We have evaluated this technique, comparing the results with those previously obtained by SB in a group of patients suspected of having PWS or AS. PATIENTS AND METHODS: Genomic DNA from 70 patients with suspected PWS or AS was used. Methylation testing by SB was carried out using the probe PW71B labeled with radioactivity. For methylation testing by PCR the DNA was treated with sodium bisulphite and hydroquinone and PCR preformed using specific primers for the maternal and paternal alleles. RESULTS: Of the 70 patients studied by PCR, 45 were normal, 17 and 8 showed altered molecular patterns that were compatible with PWS and AS, respectively. The concordance with the results obtained previously with SB was 100%. CONCLUSIONS: These data suggest that the reliability of this new technique is very good and it has advantages compared to SB, since it requires a smaller quantity of DNA and can be applied for diagnosis in newborns.

[Study of the gene of Duchenne muscular dystrophy using PCR analysis]. / Estudio del gen de la distrofia muscular de Duchenne mediante análisis con PCR.

We have performed the polymerase chain reaction (PCR) to study 26 patients affected with Duchenne muscular dystrophy as a direct diagnostic method of screening for gene deletions. We have amplified simultaneously 9 sequences which belong to 9 exons located along the two "hot spots" of the gene. We have detected deletions in many of the exons in 11 of the 26 patients (42.3% of the cases).

[Modification of the calculation of risk factors in women, possible carriers of Duchenne muscular dystrophy, based on CPK levels]. / Modificación del cálculo de riesgo en posibles mujeres portadoras de distrofia muscular de Duchenne (DMD) basado en niveles de CPK.

We have analyzed the CPK levels in 44 carriers of DMD women, previously diagnosed by using molecular techniques (from a risk population of 133 women), and compare them with the CPK levels of 138 women of a control population. The results obtained show that values higher than the normal level (> 250 mU/ml) are compatible compatible in 99% of the cases with the carrier status (21 women of the carrier population and 1 women of the control population showed values higher than 250 mU/ml). On the other hand, normal values do not distinguish between the healthy and carrier populations (22 women of the carrier population showed normal CPK levels). These results can be very useful in genetic counselling, especially in centers where it is not possible to apply recombinant-DNA techniques.

[Diagnostic value of the deletion of the delta F508 gene in cystic fibrosis]. / Valor diagnóstico de la deleción delta F508 del gen de la fibrosis quística (FQ).

We have studied 70 carrier cystic fibrosis (CF) families with delta F508 mutation using the polymerase chain reaction (P.C.R.). We found that frequency of the mutation in CF chromosomes was 53%. 39% of carrier cystic fibrosis families were informative for the mutation.

[Familial retinoblastoma: cytogenetic study of the tumor]. / Retinoblastoma familiar: estudio citogenético del tumor.

We report a case of familiar retinoblastoma, in which both mother and daughter show bilateral retinoblastoma. The cytogenetic study, in both peripheral blood lymphocytes and tumoral tissue did not show alterations on the 13 chromosome, although we found a complex kariotype in tumoral tissue defined by three celular lines. In all of them appears a marker in which the 6 chromosome is involved (der 6). The derivated of 6 chromosome are markers highly characteristic of the retinoblastoma cases, and can be related with the aggressivity of tumor and the appearance of the second tumors.

[Use of the recombinant DNA technic in studying cystic fibrosis in 14 Spanish families: detection of carriers and healthy subjects]. / Aplicación de las técnicas de ADN recombinante al estudio de 14 familias españolas con fibrosis quística: detección de portadores y sanos.

Fourteen Spanish families, containing at least one affected child with cystic fibrosis, were typed for restriction fragment length polymorphisms (RFLPs) by proper pJ3.11, pmet H and pmet D. Nine (64.3%) were fully informative for prenatal diagnosis and carrier detection; four (28.5%) were partially informative and prenatal exclusion of an affected fetus could be carried out in half of pregnancies. One (7.1%) was uninformative for these probes. Allelic frequencies obtained have also been analized, being pJ3.11 probe the most informative in our families.

[Cytogenetics of preleukemic states]. / Citogenética de los estados preleucémicos.

In about a half of preleukemic states it is possible to find chromosomal aberrations, as three n. degrees 8 chromosomes, a single n. degrees 7 or n. degrees 5 chromosome, or a partial deletion of long arm or n. degrees 5 chromosomes. From a prognostic point of view, the presence of the indicated chromosomal abnormalities show a three times increased risk to suffer leukemia. Several abnormal cell clones may be produced, but generally only one of them has the proliferative capacity to establish an evolutive non-lymphoblastic acute leukemic process.