Identification of two novel allelic variants of ESX1L in the human placenta: lack of an association with intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a leading cause of neonatal morbidity and mortality. Although epidemiological studies implicate an important role for genetic factors in determining birth weight, few candidate genes for IUGR have been identified. ESX1L, the orthologue of Esx1, is an X chromosome-linked human homeobox gene expressed in the placenta and testis. The present study was undertaken to determine if aberrations in the ESX1L gene were associated with idiopathic IUGR because targeted deletion of Esx1 in the mouse leads to abnormal placental development and consequent IUGR. Genotyping analysis of ESX1L gene was performed on placental samples from 22 normal term and 12 IUGR term fetuses. Two allelic variants were identified, and they contain an insertion and a deletion, respectively, of the same 27 nucleotides in the highly repetitive region of exon-4 that encodes the previously identified 12 contiguous repeats of a unique 9-amino acid motif, PPMAP(V/L)PPG. Thus, the insertion and deletion variants were predicted to code for an aberrant ESX1L protein containing 13 and 11 contiguous repeats, respectively. However, both variants were detectable and evenly distributed in normal as well as IUGR placentae, indicating that these two variants of ESX1L do not contribute to genetic susceptibility to idiopathic IUGR. Furthermore, no single nucleotide polymorphisms were identified, and there was no difference in the level of ESX1L mRNA between control and IUGR placentae. Taken together, these findings provide the first evidence that two allelic variants of ESX1L exist in the human placenta but they are not associated with idiopathic IUGR.     

No partial <Emphasis Type="Italic">DAZ</Emphasis> deletions but frequent gene conversion events on the Y chromosome of fertile men

Purpose: Recently, partial DAZ deletions on the Y chromosome were identified in infertile men. To determine the clinical importance of partial DAZ deletion, we studied the number of DAZ copies in a well-defined population of 47 fertile men.Methods: The number of DAZ gene copies was determined by PCR assays, qualitative and quantitative DNA blot experiments.Results: Using semi-quantitative Southern blot, no partial DAZ deletion was detected in fertile men. In many cases, the results were discordant with the PCR assays and qualitative DYS1-blot experiments suggesting that the molecular events detected by the later methods could reflect gene conversion events. Many fertile men present four copies of the DAZ genes but an atypical organization of this DAZ locus. No difference in sperm concentration and motility in the fertile men were observed according to the different DAZ-haplotypes.Conclusion: The different DAZ-haplotypes are compatible with normal spermatogenesis.     

Urinary tract malformation in the XYY male

Phenotypic expression of the 47,XYY chromosome complement in man has been investigated mostly in terms of the central nervous system. Evidence is presented here to suggest that urinary tract malformation may be a component of the XYY syndrome; this should be taken into account when counselling parents of children with this chromosome anomaly, and in making decisions when an affected foetus is diagnosed antenatally.     

Ring chromosome 7: Report of the fifth case

A 13-year-old boy with a 46,XY,r(7) karyotype presented with growth failure, microcephaly, achromic spots and multiple pigmented naevi. Psychomotor development was normal and no major malformations were present. Comparison with four previously reported patients with ring chromosome 7 shows that the most frequent findings in these subjects were short stature, microcephaly and dermatological abnormalities.     

A comparative study of immunological and cytochemical profiles between adult and childhood acute lymphoblastic leukemias (ALLs): Heterogeneity in adult common ALL

To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG-positive) for β-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p <0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with CALL (0.6 ± 0.3) was significantly lower (p < 0.01) than in the group of children with cALL (1.1 ± 0.2) or in the lymphoid-crisis group (1.5 ± 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL^?/TdT⁺) and the other with more (cALL⁺/TdT⁺). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The β-glucuronidase patterns indicate a further heterogeneity in adult ALL.     

Differential diagnosis of sonographically detected tumours in the fetal cervical region

Differential diagnosis of sonographically detected fetal neck tumours is difficult. The sonographic criteria for encephalomyelocele, lymphangioma/hygroma, teratoma, sarcoma, haemangioma, neuroblastoma and goitre are given on the basis of the authors' own observations and information from the literature. Elevation of alpha-fetoprotein in the amniotic fluid is a frequent but non-specific finding. Chromosome analysis after amniocentesis can be a useful supplementary procedure for assessing the prognosis and deciding upon the delivery procedure. Sonographic detection of a tumour in the fetal neck region enables preparations to be made for dystocia and postnatal dyspnoea of the newborn. The obstetrician must cooperate closely with paediatricians, neurologists, surgeons and ENT specialists.     

A GIRL WITH RECURRENT INFECTIONS, LOW IgM AND AN ABNORMAL CHROMOSOME NUMBER 1

A girl, now 3 years of age, is described, who since the age of 3 months had many, often severe, infections mainly caused by microorganisms with a polysaccharide structure. In addition she had very low IgM and no iso-agglutinins in her serum, and furthermore we were able to show an abnormal chromosome number 1 in more than 80% of the cells investigated from peripheral blood. The possibility that antibodies to polysaccharide antigens are directed from chromosome number 1 is referred to in this paper.     

Fetal dermatoglyphics

Dermatoglyphic studies were performed on 24 aborted human embryos in whom major chromosomal aberrations had been revealed by amniocentesis. Prints were obtained from the embryos by the Hollister method. An analysis was done using patterns on finger tips and the atd angle was measured in degrees. The Penrose classification was used to describe the locations of the various palm and foot patterns. Twenty-two out of the 24 embryos showed dermatoglyphic deviations that correlated well with the cytogenetic diagnosis. The fetuses had the following disorders: 7 with trisomy 21, 2 with trisomy 18, 2 with trisomy 13, 3 with structural autosomal aberrations and 10 had a sex-chromosome aberration.     

Inhibition of human leukemia cell proliferation by dimethyl sulfoxide

The treatment with 1% and 2% DMSO produced reversible structural and functional changes in the K-562 human myelogenous cell line. These changes include: (a) inhibition of cell proliferation with decreased RNA and DNA syntheses; (b) morphological features that are compatible with less primitive leukemia cells; (c) diminished plating efficiency in agar; and (d) loss of their malignancy as determined by the capacity of K-562 cells to develop myelosarcomas in lasat mice. The cytochemical pattern and antigenic markers of the leukemic cells were not modified by treatment with DMSO. These results suggest that the effect of DMSO on K-562 cells is consistent with cytotoxicity rather than a stimulation of cell differentiation.