Antenatal Diagnosis of De Novo Balanced Structural Chromosome Aberrations in Latin America

Abstract

INTRODUCTIONThe consequences of de novo balanced structural chromosome aberrations diagnosed antenatally are unpredictable, and, as a result, they introduce uncertainty into genetic counseling decisions.OBJECTIVE Describe de novo balanced structural aberrations present at antenatal diagnosis in samples from pregnant women in fi ve Latin American countries and determine their effect on carrier individuals. METHODSThis was a retrospective observational study based on analysis of 109,011 antenatal tests conducted from January 1981 to December 2016 in Cuba, Uruguay, Costa Rica, Mexico, and Colombia. Thirteen cytogenetic laboratories provided information that included the cases analyzed during the study period; number of de novo balanced structural aberrations diagnosed antenatally; number of diagnoses with de novo balanced structural aberrations that resulted in termination of pregnancy; detailed descriptions of the karyotypes of de novo balanced structural aberration carriers, and descriptions of the form of diagnosis, including types of samples used (amniotic fl uid, chorionic villus or fetal blood). Each laboratory also provided pathology reports and genetic counseling at time of diagnosis. Postnatal followup for pregnancies carried to term continued for at least two years. RESULTSOf the 109,011 antenatal tests studied, 72 (0.07%) showed de novo balanced structural aberrations. These events primarily involved chromosomes 1, 2, 7, 14, 18, and 20. Of the 79 breakpoints identifi ed, the most common were 5p15.3, 7q11.2, 7q22, and 14q24. We identifi ed three breakpoints corresponding to 3.8% (3q13.1, 3q13.2, and 9p12) that were not reported in other studies of de novo balanced structural aberrations diagnosed antenatally in patients from other geographic regions or in studies of chromosomal fragile sites. Two of these breakpoints (3q13.1 and 3q13.2) were associated with high risk of phenotypic abnormalities. Information on antenatal or postnatal followup was available for 62 (86%) of de novo balanced structural aberration carriers; of the 44 carriers with postnatal followup, 10 had phenotypic abnormalities.CONCLUSIONS Three new de novo breakpoints were identifi ed, presumably related to genetic admixture characteristics in Latin America. Since some diseases associated with de novo balanced structural aberrations detected antenatally have a late onset, followup for at least two years is recommended for carriers of these aberrations. The information in this study is useful in genetic counseling for pregnant women in Latin America.

Rearreglos cromosómicos complejos involucrados en la infertilidad masculina

“…(4) También en los hombres puede provocar alteraciones en la espermatogénesis (azoospermia o oligoasthenoteratospermia) y espermatozoides con desbalances cromosómicos que resultan en abortos tempranos a repetición y niños con múltiples anomalías congénitas. (4,5) UnRCC en una familia generalmente surge como un solo evento complejo, en lugar de cambios secuenciales, en una meiosis durante la gametogénesis masculina. [8][9][10][11][12] En el individuo fenotípicamente anormal, presumiblemente existe algún desequilibrio submicroscópicoen los puntos de ruptura o existe otro defecto genético sin detectar, y estos casos, en su mayoría, involucran una anomalía cromosómica de novo.…”