Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1

Abstract

PurposeThe purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband—namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)—and to compare data of the pedigree analyses performed by direct method.MethodsThree-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed.ResultsSimilar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %—comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1–4p 16.3 region.ConclusionsRevealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

Limited survivability of unbalanced progeny of carriers of a unique t(4;19)(p15.32;p13.3): a study in multiple generations

“…The frequencies of particular forms of unbalanced gametes produced by carriers of a balanced RCT are contingent on several factors including the size of chromosomal segments involved, their genetic content, sex of RCT carrier, and location of chromosome breakpoints. Survival of progeny with particular imbalances plus possibly other factors influence the risk estimation for the individual RCT carrier [ 5 , 32 , 33 ]. Therefore each empirical study is useful for genetic counseling.…”

“…Apart from the essential underlying chromosome aberration, monosomy 4p, WHS may also be due to a double segment imbalance with monosomy 4p included, resulting from meiotic malsegregation of a parental reciprocal chromosome translocation (RCT). In such cases the imbalance of the partner chromosome segment may impact the phenotype, so the clinical diagnosis of WHS may be “biased” by that effect [ 2 , 5 ].…”

Monosomía 9p24 secundaria a translocación (2;9) en dos pacientes no relacionadas

“…2 Por lo general, los portadores balanceados tienen fenotipo normal; sin embargo, pueden presentar infertilidad, abortos o descendencia con malformaciones congénitas por la formación de gametos desbalanceados. En ocasiones, los portadores tienen un fenotipo anormal, debido a un defecto monogénico por disrupción de un gen. 3 La monosomía del brazo corto del cromosoma 9 (9p) es poco frecuente; se caracteriza por RDPM, trigonocefalia, dismorfias faciales y anomalías genitales. 4,5 En el diagnóstico de las cromosomopatías, se utilizan diversos estudios, como el cariotipo con bandas G por tripsina y tinción con giemsa (GTG) o la hibridación in situ con fluorescencia (fluorescent in situ hybridization; FISH, por sus siglas en inglés), que detecta aberraciones en regiones específicas.…”

Caracterização de uma amostra de indivíduos com deficiência intelectual de origem indeterminada

“…Tabela 16. Características clínicas encontradas no paciente P166 em comparação com sinais fenotípicos típicos em indivíduos com deleção 4p e duplicação 8p (adaptado de Zollino et al 168 , South et al 161 , Midro et al 195 , Dai et al 196 ). Tabela 17.…”

“…Comparando-se o quadro clínico da paciente P124 com a descrição dos dismorfismos mais comuns em monossomia 4p e trissomia 12p, observam-se similaridades entre as condições (Tabela 15) 154,155,172,194 Quanto a rearranjos envolvendo as regiões 4pter e 8pter, há vários relatos na literatura 168,195,196 . A trissomia 8p é caracterizada por hipotonia, DI, baixa estatura, dificuldade de alimentação, hipertelorismo, ponte nasal alargada, lábios volumosos, dentição anormal e orelhas dismórficas 197 .…”