[Clinical, cytogenetic and molecular characterization of a new case of Nijmegen breakage syndrome in Chile]. / Caracterización clínica, citogenética y molecular de un nuevo caso de síndrome de Nijmegen en Chile.

The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder associated with microcephaly, immunodeficiency, chromosome instability and cancer proneness. The mutated gene that results in NBS codes for nibrin (Nbs1/p95), a DNA repair protein that is functionally linked to ATM, the kinase protein product of the gene responsible of ataxia-telangiectasia (A-T). We report the clinical, cytogenetic and molecular characterization of a second case of NBS in Chile detected by us. The patient is a 7 year old Chilean boy from a consanguineous marriage, with microcephaly, immunodeficiency and acute non lymphocytic leukemia (ANLL). As NBS shares chromosomal and cellular features with A-T, the cytogenetic studies of this patient also included 3 A-T patients. Our results showed that the frequency of spontaneous and X rays induced chromosomal aberrations in NBS are higher than in A-T cells. DNA analysis revealed that the patient is homozygous for the Slavic mutation 657del5 in the NBS1 gene. This finding and the absence of nibrin in patient's cells, confirmed the clinical diagnosis of NBS in our patient.

First-trimester sonographic diagnosis of holoprosencephaly: value of the "butterfly" sign.

OBJECTIVE: To study the value of choroid plexus dysmorphology as a screening tool for the first-trimester sonographic diagnosis of holoprosencephaly in a high-risk population. METHODS: A total of 378 consecutive pregnancies undergoing chorionic villus sampling between 11 and 14 weeks' gestation were scanned before the procedure, following the recommendations of the Fetal Medicine Foundation (London, England). A cross-sectional view of the fetal brain, including the visualization of both choroid plexuses (the "butterfly" sign), was obtained in all cases. RESULTS: There were 3 cases in which the butterfly sign was not identified. In these cases, the first-trimester diagnosis of holoprosencephaly was confirmed by the presence of a single monoventricular cavity and fused thalami. Two of these fetuses had features of facial dysmorphism at the time of presentation and 2 had extracranial anomalies, including a cystic hygroma in 1 and a small omphalocele and polydactyly in another. Chromosomal analysis showed trisomy 13 in 2 cases and a ring chromosome 13 in the other. CONCLUSIONS: This series suggests that failure to identify the butterfly sign is a warning sign of holoprosencephaly in the first trimester. Systematic identification of the butterfly sign at the time of sonographic assessment of nuchal translucency provides a valuable tool for the early screening of holoprosencephaly.

Second-trimester sonographic findings in trisomy 22: report of 3 cases and review of the literature.

OBJECTIVE: To describe cases of trisomy 22 detected prenatally on second-trimester sonography and to review the literature on similar cases, with special emphasis on the prenatal findings and pregnancy outcome. METHODS: We performed follow-up second-trimester sonography and fetal karyotyping on 3 pregnant women who were referred because of abnormal findings on initial second-trimester scans. We also conducted a literature search for other reports of sonographic findings in trisomy 22. RESULTS: Fetal abnormalities shown on sonography included nuchal thickening, mild generalized skin edema, an atrioventricular septal defect, an interventricular septal defect, edema of the scalp, face, and neck, severe left pleural effusion with a marked mediastinal shift, ascites, agenesis of the diaphragm, ambiguous genitalia, a single umbilical artery, bradycardia, a multicystic left kidney, and an absent right kidney. All 3 fetuses had karyotypes indicating trisomy 22. One pregnancy was terminated at the parents' request, and 2 ended in fetal death at 23 and 26 weeks. Our literature search revealed only 1 previous report of second-trimester sonographic diagnosis of trisomy 22. We found 3 other reports describing prenatal diagnosis in the third trimester, but only limited information on the sonographic findings was available. CONCLUSIONS: Second-trimester sonography provides valuable clues for the prenatal diagnosis of several chromosomal disorders, including trisomy 22. Prenatal karyotyping is warranted if fetal growth restriction is detected in the second trimester, especially if associated with congenital defects.

[Effect of vitamin E (DL-alpha-tocopherol) on the frequency of chromosomal damage in lymphocytes from patients with ataxia telangiectasia]. / Efecto de la vitamina E (DL alpha-tocoferol) sobre el daño cromosómico en linfocitos de pacientes con ataxia telangiectasia.

BACKGROUND: In ataxia telangiectasia (A-T), the lack of a functional ATM kinase is associated with disturbances in the processing of DNA damage and a chronic oxidative stress. These disturbances may be responsible for an increment of chromosomal damage in A-T cells. AIM: To study the in vitro effect of vitamin E (DL-alpha-tocopherol) on the frequency of chromosomal damage of lymphocytes from patients with A-T. PATIENTS AND METHODS: Seven patients with A-T and age-sex matched controls were studied. Chromosomal damage in mitosis was evaluated in lymphocytes cultures both under basal conditions and when G2 repair was prevented by 5 mM caffeine. RESULTS: In cells from patients with A-T, vitamin E induced a 57.1 and 47.9% decrease in chromosomal damage under basal and inhibited G2 repair conditions, respectively. However, there was a non significant improvement in their repair activity. Vitamin E effects on chromosomal damage was not significant in control subjects. CONCLUSIONS: Vitamin E reduces chromosomal damage in lymphocytes from patients with ataxia telangiectasia.

Cromatina de Barr: análisis de su valor actual / The Barr chromatin: analysis of its current value

Entre los años 1980 y 1985 se hicieron estudios de cromatina X en 610 individuos. En 321 varones había cuerpos de Barr en las células de 27 individuos; en 18 de ellos se estudiaron los cariotipos, encontrándose un segundo cromosoma X en casi todos, con sólo dos excepciones que tenían sólo 2% de positividad. Un recién nacido con genitales externos ambiguos y 27% de cuerpos de Barr positivos resultó ser un hermafrodita verdadero (46,XX). En tres de 25 niñas recién nacidas no se detectaron cuerpos de Barr, sus cariotipos resultaron 45,X en dos de ellas. La proporción de células positivas en los recién nacido fue ligeramente menor que en edades posteriores. Entre 263 mujeres mayores que 1 mes de edad, 175 tenían 20% o más de cromatinas positiva. En dieciséis mujeres se obtuvieron resultados negativos, los cariotipos se estudiaron en 13 y fueron todos anormales. Setenta y dos mujeres tuvieron cromatinas sexuales positivas en niveles inferiores que 20%, 38 fueron estudiados con cariotipo y en 11 éste resultó alterado. En este grupo se observó que mientras menor era la proporción de cuerpos de Barr presentes, mayor era la incidencia de anomalías del cromosoma X

Estudio citogenético en parejas con pérdida reproductiva / Cystogenetic study in couples reproductive loss

El estudio citogenético en parejas con pérdida reproductiva es una valiosa herramienta que permite establecer su causa, estimar el riesgo de recurrencia del aborto o prevenir el nacimiento de un hijo defectuoso. Estudiamos 20 parejas con historia de pérdida reproductiva y encontramos dos individuos (10% de las parejas) con una translocación autosómica balanceada y dos mujeres con un mosaicismo de los cromosomas X. En 20 parejas control encontramos sólo una mujer con mosaicismo de los cromosomas X. No hubo diferencias significativas en la incidencia de sitios frágiles ni en los polimorfismos de la heterocromatina de los cromosomas 1, 9, 16 e Y

Síndrome de Down: una forma inusitada de mosaicismo / Down's syndrome: an unusual form of mosaicism

Se presenta el caso de una niña con un síndrome de Down atenuado cuyo cariotipoes: 46,XX, del (21) (qter-cen:0/46,XX-21 + i (21) (qter-cen-qter). El cariotipo de ambos padres es normal. Se discute el origen de ambas líneas celulares y el mecanismo de formación del isocromosoma