Pericentric inversions of chromosome 4: report of a new family and review of the literature

A family was cytogenetically studied because of the birth of a male child with a multiple congenital anomaly pattern, in whom a dup (4q) recombinant was found. His phenotypically normal mother's karyotype showed an apparently balanced pericentric inversion in a chromosome 4. So as to analyze the occurrence of recombinants, the cytogenetic data from this family are compared with those of the 18 previously reported familial cases of pericentric inversions (PIs) of chromosome 4. The congenital anomalies observed in the child strongly suggest Wolf-Hirschhorn syndrome but some of his clinical features seem to be pathogenetically related to the presence of lymphedema during the intrauterine period. In the multiple congenital anomaly pattern observed in this patient, the lymphedema could be the consequence of the large 4q duplication. The review of chromosome 4 PIs with 4q duplication suggests that the q3 region should be examined when edema is detected prenatally.     

The prognostic role of the extent of Y microdeletion on spermatogenesis and maturity of Sertoli cells

Substantial involvement of the Y chromosome in sexual development and spermatogenesis has been demonstrated. Over the last decade, varying extent of Y chromosome microdeletions have been identified among infertile patients with azoospermia or oligozoospermia. These microdeletions were clustered in three main regions named AZFa, AZFb, and AZFc. Analysis of the Y chromosome microdeletion was found to be of prognostic value in cases of infertility, both in terms of clinical management as well as for understanding the aetiology of the spermatogenesis impairment. However, the accumulated data are difficult to analyse, due to the variable extent of these deletions, the different sequence-tagged sites (STS) used to detect the microdeletions, and the non-uniformity of the histological terminology used by different investigators. This debate discusses the chances of finding testicular spermatozoa in men with a varying extent of Y chromosome microdeletions. The genotype and germ cell findings in men with AZFa microdeletions as well as those that include more than a single AZF region are reviewed, as is the effect of Y chromosome AZF microdeletions on the maturity of the Sertoli cells.     

Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation: case report

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.     

Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.     

Mitochondrial DNA and Y-Chromosome Variation in the Caucasus

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y‐haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male‐mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001     

香烟烟雾提取物致小鼠生殖细胞的遗传学损伤

目的：研究香烟烟雾提取物对小鼠生殖细胞染色体和精子的影响,方法：给雄性小鼠腹腔注射不同剂量的香烟烟雾提取物,观察其精原细胞染色体畸变及精子畸形的情况,结果：精原细胞染色体畸变率及精子畸形率均增高,精子畸形率增高的程度大于精原细胞染色体畸变率。结论：香烟烟雾提取物可致雄性小鼠生殖细胞染色体畸变和精子畸形。     

Further evidence for the location of the blepharophimosis syndrome (BPES) at 3q22.3-q23

Fryns JP, Strømme P, van den Berghe H. Further evidence for the location of the blepharophimosis syndrome (BPES) at 3q22.3-q23.
Clin Genet 1993: 44: 149–151. © Munksgaard, 1993
We report a 6-year-old, mentally retarded boy with typical clinical signs and symptoms of the blepharophimosis syndrome ( b lepharophimosis, p tosis, e picanthus inversus s yndrome (BPES)), born to normal parents. Chromosome studies revealed an interstitial deletion in the long arm of chromosome 3: del(3)(q22.3—q23). This observation reinforces previous suggestions that the location of the BPES gene is at 3q2, i.e. 3q22.3-q23.     

染色体变异与男性不育

目的 探讨染色体异常与男性不育的关系。方法 对565例男性不育患者进行染色体分析。结果 发现染色体异常69例,异常率为12.21%。其中性染色体异常48例,占异常核型 69.75%;性反转综合征1例,占异常核型1.45%;常染色体异常20例,占异常核型28.98%。结论 染色体异常是造成男性不育的重要遗传因素。提示对精液检查异常者或男性性征发育不良者进行染色体检查,将有助于不育病因的诊断。