Constitutional chromosome anomalies in patients with cerebral gigantism (Sotos syndrome)

Two boys are presented with the clinical features of cerebral gigantism and chromosomal variants which have not been described so far in this syndrome. In the first boy a de novo pericentric inversion of chromosome Y was found, the karyotypes of all other investigated family members were normal. The patient had an obstructive hypertrophic cardiomyopathy and atrial septal defect type II. The second boy had inherited pericentric inversion of the heterochromatic region of chromosome 9 from his mother. This chromosome 9 variant was also found in his sister who had a similar phenotype but without gigantism. Endocrine evaluation demonstrated normal results in both boys. The intellectual achievement in both cases was average.     

On the effect of mebendazole on metacestodes of Mesocestoides corti and Echinococcus multilocularis (author''s transl)

Human chromosome 9 shows a high susceptibility for structural rearrangements, particularly pericentric inversions, which often are transmitted. Three types of pericentric inversions can be observed on No. 9: 1) Type I, showing the total constitutive heterochromatin in the short arm. 2) Type II with part of the C heterochromatin on the short arm, the rest located on the long arm proximal to the centromere. 3) Type III: a subtelocentric chromosome with part of the C heterochromatin in the very short arm and the rest located interstitially on the long arm. With these inversions as well as with other structural rearrangements, e.g. translocations, the break-points are located preferentially within the C heterochromatin or close to the heterochromatic-euchromatic junctions. These findings are in contrast to the findings in lymphocytes from 5 patients with fancomi's and after irradiation in vitro, reported in the literature. In lymphocytes break-points seem to be distributed more or less by chance. These observations together led us to speculate that human chromosome 9 primarily was an acrocentric chrosome; in morphology and at least in some functions similar to D- and G-group chromosomes. During evolution this acrocentric chromsome changed to a submetacentric one due to a pericentric inversion.     

Adaptation to the mental health setting: the lived experience of comprehensive nurse graduates

Karyotype analysis of a primary culture from a case of papillary thyroid cancer (PTC) showed an abnormal short arm of one homologue of chromosome 2 as sole abnormality in 4 of 16 metaphases. Based on G-banding analysis, two different aberration types on chromosome 2 could be assumed representing either a del(2)(p22-23) or a pericentric inversion. Further comparative genomic hybridization (CGH) analysis as well as fluorescence in situ hybridization (FISH) analysis were performed to confirm the assumed alterations. While CGH analysis showed no loss of chromosome 2 material, FISH with yeast artificial chromosome (YAC) probes homologous to the region 2p22-23 demonstrated two pericentric inversions of chromosome 2 involving different breakpoints on 2p in 6.8% and 4.2% of the metaphases, respectively. Polymerase chain reaction (PCR) analysis with degenerated oligonucleotide primers that bind within the conserved catalytic domain of tyrosine kinase (tk) genes resulted in amplification products with DNA of YAC 851D11 suggesting the presence of such genes at or near the translocation breakpoint.     

Variants of chromosome 9 in phenotypically normal individuals

The human chromosome 9 displays the highest degree of structural variability. Four different types of variants are described including pericentric inversion, extra G-positive band in the q arm, additional G-positive band in the p arm and duplication of band 9q21-q22. It is important to demonstrate inheritance from a phenotypically normal individual in order to differentiate between a variant chromosome and an abnormal chromosome.     

Inversion (X)(p11.4q22) associated with Norrie disease in a four generation family

We report on a 4-generation family in which Norrie disease occurs together with a pericentric inversion of the X chromosome in all affected males and carrier females. The breakpoint in the short arm of the X chromosome appears to be at the purported location of the Norrie disease gene. This is the second report of an association between Norrie disease and a chromosome aberration involving Xp11, and the first report of a specific gene disruption, thus physical gene location, due to a pericentric chromosome inversion.     

Homozygosity for pericentric inversions of chromosome 9. Prenatal diagnosis of two cases

The finding of homozygosity for a pericentric inversion of chromosome 9 [inv(9)] is rare, and previously has not been reported at prenatal diagnosis. We describe two unrelated cases of homozygosity for inv(9) identified in amniocytes. In each case, both parents were heterozygotes for the inv(9); 46,XX,inv(9)(p11q13) and 46,XY,inv(9) (p11q13). Case 1 resulted in a normal term infant who at age 5 years was phenotypically and developmentally normal. Case 2 was referred for severe intrauterine growth retardation (IUGR) and oligohydramnios, and subsequently expired in utero. Even though inv(9) is a normal chromosome variant with a frequency of 1 to 3% in the general population, the finding of homozygosity for inv(9) and IUGR in this fetus suggested the possibility of uniparental disomy (UPD). Molecular studies confirmed the presence of both parental inv(9) chromosomes, excluding the possibility of chromosome 9 UPD as the cause of IUGR in this fetus. Presumably, inv(9) homozygosity results from the high frequency of inv(9) heterozygosity, and is a normal variant. However, until the effects of UPD for chromosome 9 are established, parental karyo types and, where appropriate, molecular studies should be performed to exclude UPD. In addition, more reports of inv(9) homozygosity detected prenatally are needed to assess its frequency and outcome.     

Chromosome variation and anomalous karyotypes in the red-backed mouse Clethrionomys rufocanus (Rodentia, Microtinae)

G-banding and C-banding of chromosomes were studied in populations of the red-backed mouse Clethrionomys rufocanus from 11 localities of eastern Russia. Intrapopulation polymorphism of autosome 3 caused by the deletion-duplication of the short-arm heterochromatin (2n = 56; NFa = 56-58) was demonstrated. The karyotype of Cl. rufocanus from continental populations and Sakhalin Island was shown to have a large subtelocentric chromosome of pair 3 (NFa = 58), whereas in the population from Kunashir Island, chromosomes of this pair were acrocentric (NFa = 56). One animal from the population of the Kedrovaya Pad' Reserve (Primorsk krai) had a pericentric inversion (acrocentric morphology) of the Y chromosome. In two animals, a female from the Ussuriiskii Reserve (Primorsk krai) and a male captured near the Tomari Settlement (Sakhalin Island), a pericentric inversion of one chromosome of pair 6 was found (NFa = 59). The inversion detected in the animal from the Sakhalin population was accompanied by the loss of the centromeric heterochromatin. In contrast, the inversion of the chromosome pair 6, which was found in the mouse from the Primorsk krai population, did not involve the loss of centromeric heterochromatin. Analysis of our results and data from the literature showed that the karyotype of Cl. rufocanus is not constant, as was thought earlier. The percentage of animals with abnormal karyotype (1.6%) was higher than in other groups of red-backed mice studied (0.12-0.7%).     

All roads lead to Rome? The multiple pathways of protein folding

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.     

Constitutional mosaicism for a chromosome 9 inversion resulting in recombinant aneusomy in an offspring

We report on a case of constitutional mosaicism for a large pericentric inversion of chromosome 9 in a man whose daughter had recombinant aneusomy resulting in partial 9q duplication and partial 9p deletion. At age 6 months, the girl was evaluated because of congenital anomalies [corrected] and developmental delay. Chromosomal analysis on this infant showed a derivative chromosome 9 which was later determined to be a recombinant chromosome with trisomy of 9q34.1-->qter and monosomy of pter-->9p24. Chromosomal analysis in her father showed the presence of two cell lines; 75% of lymphocytes had a 46,XY pattern, and 25% had a 46,XY,inv(9)(p24q34.1) karyotype. The infant's physical findings represent a composite of the reported cases of both trisomy 9q34.1-->qter and monosomy pter-->9p24. The infant's father was phenotypically and cognitively normal. This case broadens the spectrum of reported cases of mosaicism for an autosomal structural rearrangement generating unbalanced gametes, and further supports the tenet that constitutional mosaicism has clinical relevance for genetic counseling.     

Observations on the pia-arachnoid of the anterior median fissure and the posterior median sulcus of the fetal spinal cord of the albino mouse

A pericentric inversion of an X chromosome [46,X,inv(X)(p11q28] with no detectable deletions was ascertained by amniocentesis for prenatal diagnosis in a 42-year-old woman. No defintive counsel could be offered as such an inversion had not been previously reported. At 1 year, the infant appears normal. These data and the review of other recently published karyotypes suggest an absence of a somatic position effect in the human X chromosome and possible biases of ascertainment or possible alternative karyotypic interpretations of some previously reported inv(X) cases.     

Commentary: tensions between the theory and practice of palliative care

Structural variations between great ape and human chromosomes due to pericentric inversions and translocations have created at apparent controversy during the reconstruction of hominoid phylogeny. One such variation involves human chromosome 5, which is equivalent to chromosome 4 in chimpanzee and orangutan but equivalent to segments of chromosomes 4 and 19 in gorilla. Obviously, neither banding patterns nor centromeric indecies in these chromosomes match. The pathological condition of cri du chat syndrome is due to the cytogenetic deletion of band p15.2 of chromosome 5. Is this region involved during pericentric inversion of apes chromosome 4? We used a human cosmid probe for cri du chat syndrome as a phylogenetic marker in search of the aforementioned question. The genomic sequences for cri du chat syndrome region were conserved in chimpanzee (PTR4) and orangutan (PPY4) but displayed a positional divergence in gorilla on chromosome 19(GG019). In addition, we used a human cosmid DNA probe for DiGeorge syndrome which is located on chromosome 22 band q11.2 and was conserved within band 23q11.2 in apes. The loci specific human genomic probes may help to describe the inversions and translocations for other chromosomes.     

Laryngocele: clinical and therapeutic study of 60 cases

Sixty patients with laryngocele were diagnosed in the last seven years: 25 of them without previous laryngeal pathology (group A) and the rest 35 with laryngeal or pharyngeal cancer (group B). The laryngocele was unilateral in the majority of the 25 patients of group A (68%). The internal laryngoceles were the most common type (63%). The initial symptom was hoarseness in 56% of these patients and 20% developed, in their evolution, an acute respiratory distress. The diagnosis was clinical in 16 patients and radiological in the rest. Endoscopically marsupialization with laser-CO2 was performed to remove internal laryngoceles. The mixed and external laryngoceles were completely removed via an external cervical approach without the need to perform any thyrotomy. The diagnosis was radiological by CT in the 35 patients of the group B. In 30 of them the CT was performed to evaluate the local extension of the laryngeal or pharyngeal cancer before its treatment. Supraglottic carcinoma was the most common laryngeal tumor (50%). The anatomic relationship between laryngocele and laryngeal cancer was ipsilateral to each other only in 50% of the patients. In the other 5 patients, no laryngocele was found in the radiological study previous to the treatment of the laryngeal or pharyngeal cancer. The diagnosis was made after chemotherapy and/or radiotherapy treatment.     

Repetitive DNA sequence families in Crepis capillaris

Three families of tandemly repetitive DNA from Crepis capillaris were cloned and characterized. Data obtained from in situ hybridization indicate that these families are located mainly in the heterochromatic C-bands. The pCcH32 family hybridizes at the paracentromeric C-band of the NOR (nucleolus-organized region) chromosome and along most of the long arm of the same chromosome. The pCcD29 family is located in all the remaining C-bands of the karyotype, while the third family, pCcE9, is restricted to the more proximal C-bands. Nucleotide sequence comparisons between one cloned repeating unit from each DNA family showed some significant regions of homology between the families. We discuss the sequence relationships between the three DNA families and the significance of our data in relation to models of heterochromatin evolution, emphasizing the concepts of equilocality and the differentiation of the NOR-bearing chromosome. We also examine the possible role that chromosome disposition, in either mitotic or meiotic nuclei, plays in the distribution and homogenization of heterochromatic DNA sequences.     

Somatic pairing and meiotic nonrandom disjunction in a pericentric inversion of Hylemya antiqua (Meigen)

An asymmetrical pericentric inversion in the onion fly, Hylemya antiqua was studied. Somatic pairing was studied in young eggs from test-and sibcrossed inversion heterozygous females which gave four and seven distinguishable karyotypes respectively. From these seven, three are balanced: the normal type, the inversion heterozygote and homozygote, and four are unbalanced recombinant karyotypes descending from crossovers in the loop. In all types at all mitotic stages the centromeres are paired. The telomeres only show association during prophase but this decreases from mid to late prophase. Quantitative analysis of the four different crossover products as produced by inversion heterozygous females showed the presence of nonrandom disjunction. A significant disparity was observed, viz. the normal chromosome was taken up preferentially into the functional gamete compared to the inverted chromosome. Dragging of long chromatids in the asymmetric dyad during M I-A I is a possible explanation of this feature.     

Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy?

PURPOSE: To determine if pretreatment computed tomography (CT) can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Forty-two patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes and extent were determined by consensus of two head and neck radiologists on pretreatment CT studies. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. Sclerosis of any laryngeal cartilage was recorded. The specific CT parameters assessed were correlated with local control. RESULTS: Tumor volume was a significant predictor of local control. For tumors measuring < 3.5 cm3, local control was achieved in 22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of anatomic extent was also found to be a significant predictor of local control. The local control rate for tumors assigned a low tumor score (< or = 5) was 78% (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6, 7, or 8) (p = 0.008). A significant decrease in the local control rate was observed for cancers involving the paraglottic space at the false vocal cord level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020). There were 12 patients with sclerosis of both the ipsilateral arytenoid and the adjacent cricoid cartilage. These patients showed a significant decrease in local control (4 of 12 [33%]). CONCLUSION: Pretreatment CT can stratify patients with T3 glottic carcinoma into groups more or less likely to be locally controlled with definitive RT. The local control rate for these tumors can be improved using a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage sclerosis.     

Detection of human papillomavirus DNA in laryngeal squamous cell carcinoma by polymerase chain reaction

Although human papillomaviruses (HPVs) have been found in many, but not all, tumours of the oral cavity, nose, pharynx and larynx, the true role of HPV in malignant tumours of the head and neck is still unclear. The presence of HPV DNA was investigated in 45 fresh squamous cell carcinoma (SCC) specimens and in 29 normal mucosa specimens collected from 45 primary laryngeal SCC patients. HPV DNA was detected using the polymerase chain reaction (PCR) with consensus primers that detect HPV types 6, 11, 16 and 18.9 of the 45 patients (20%) were HPV positive; the presence of HPV was also detected in the corresponding normal laryngeal mucosa of four of the 29 specimens (14%). No statistically significant differences were found between the presence of HPV DNA in normal specimens and in neoplastic mucosa specimens. No correlation was found between HPV DNA positive tumours and size, T classification, lymph node involvement and histological grading. This study adds further evidence suggesting a possible role of HPV DNA infection in laryngeal carcinogenesis.     

Growth arrest and suppression of tumorigenicity of bladder-carcinoma cell lines induced by the P16/CDKN2 (p16INK4A, MTS1) gene and other loci on human chromosome 9

Wild-type P16/CDKN2 (p16INK4A, MTS1) cDNA, directed by the cytomegalovirus (CMV) immediate early promoter, was transfected into RT4 and RT112 bladder-carcinoma cell lines bearing a mutated endogenous P16/CDKN2 gene and lacking endogenous P16/CDKN2 respectively. In both cases, only transfected clones with rearranged exogenous P16/CDKN2 cDNA could be grown and propagated in cell culture. This result is reminiscent of transfection of wild-type p53 into cells with a deleted or mutated endogenous gene and suggests that P16/CDKN2, over-expressed under control of the strong CMV promoter, induces growth arrest in RT4 and RT112 cells. Transfer of human chromosome 9 to RT4 cells produced RT4/H9 hybrid clones retaining the P16/CDKN2 gene, since in RT4/H9 cell clones P16/CDKN2-gene expression is modulated by the physiological control of chromosomal regulatory sequence. All the RT4/H9 clones lost the entire chromosome 9, except clone 4 and clone 5, which maintained a deleted and an intact chromosome 9 respectively. Loss of several loci in 9p21, including P16/CDKN2, in tumors induced in nude mice by clone 4 and clone 5 suggests that P16/CDKN2 or other genes in 9p21 suppress tumorigenicity in bladder-carcinoma cells. Tumors induced by clone 4 and clone 5 show loss of markers in 9q. The regions 9q22.3, 9q32-33 and 9q34.2, which were maintained in the 2 clones and lost in their derived tumors, may contain tumor-suppressor genes relevant in bladder carcinoma. The results of this study suggest that the P16/CDKN2 gene controls growth of bladder-carcinoma cells when it is over-expressed, and may be involved in the development of bladder carcinoma, but other genes in 9p21 and 9q may participate in bladder-cancer progression.     

Prenatal exclusion of segmental trisomy in familial chromosome 21 pericentric inversion by fluorescence in situ hybridization

We report the prenatal exclusion of partial trisomy in a family with maternal pericentric inversion of chromosome 21 by fluorescence in situ hybridization (FISH). After determining the structural rearrangement in the mother and her affected son with 46,XY,rec(21)dup(21q)inv(21)(p11q22) resulting in Down syndrome (DS), a chorionic villus sample from the current pregnancy was analysed for the copy number of the DS critical region with a cosmid contig. The signal distribution was normal and the cytogenetic analysis revealed that the fetus had inherited the inverted chromosome 21 in a balanced form. FISH probes specific for the DS region are of great value in supporting cytogenetic results, regardless of the structural status of chromosome 21.     

The physical relationship of barley chromosome 5 (1H) to the linkage groups of rice chromosomes 5 and 10

Using a recently developed polymerase chain reaction (PCR)-mediated approach for physical mapping of single-copy DNA sequences on microisolated chromosomes of barley, sequence-tagged sites of DNA probes that reveal restriction fragment length polymorphisms (RFLP) localized on the linkage maps of rice chromosomes 5 and 10 were allocated to cytologically defined regions of barley chromosome 5 (1H). The rice map of linkage group 5, of about 135 cM in size, falls into two separate parts, which are related to the distal portions of both the short and long arms of the barley chromosome. The markers on the rice map of chromosome 5 were found to be located within regions of the barley chromosome which show high recombination rates. The map of rice chromosome 10, of about 75 cM in size, on the other hand, is related to an interstitial segment of the long arm of chromosome 5 (1H) which is highly suppressed in recombination activity. For positional cloning of genes of this homoeologous region from the barley genome, the small rice genome will probably prove to be a useful tool. No markers located on rice chromosomes were detected within the pericentric Giemsa-positive heterochromatin of the barley chromosome, indicating that these barley-specific sequences form a block which separates the linkage segments conserved in rice. By our estimate approximately half of the barley-specific sequences of chromosome 5 (1H) show a dispersed distribution, while the other half separates the conserved linkage segments.     

Frequent loss of heterozygosity on chromosome 9 in adenocarcinoma and squamous cell carcinoma of the esophagus

Loss of heterozygosity (LOH) affecting chromosome 9p has been shown to occur frequently in head and neck cancer, glioma, mesothelioma, melanoma, lung cancer, and numerous other tumor types. Chromosome 9p is therefore presumed to contain a tumor suppressor gene or genes. Since esophageal cancer shares characteristics with some of the above tumor types, we performed a detailed examination of 60 patients with squamous cell carcinoma or adenocarcinoma of the esophagus for LOH at loci D9S162, IFNA, D9S171, D9S126, D9S104, D9S165, and D9S163. Multiplex polymerase chain reactions were performed with the inclusion of one radiolabeled nucleotide, and products were electrophoresed on denaturing polyacrylamide gels. Thirty-six of the 60 patients (60%) exhibited LOH at one or more loci on chromosome 9p. Eight of 17 patients (47%) with adenocarcinoma manifested LOH, while 28 of 43 (65%) with squamous cell carcinoma showed LOH. LOH was most frequent at loci D9S171 (19 of 23, or 83%) and D9S165 (24 of 32, or 75%). These data support the hypothesis that a tumor suppressor gene or genes located on this portion of chromosome 9p exert(s) an effect on esophageal cancer development.