Derivative chromosome 11 in a child resulting from a complex rearrangement involving chromosomes 3, 6 and 11 in father: Significance of parental karyotyping.

The presence of derivative chromosome in a child with phenotypic features necessitates the need of parental karyotyping to ascertain the exact amount of loss or gain of the genetic material. The aim of this study was to emphasize the importance of parental karyotyping. Cytogenetic evaluation of the proband and his father were carried out at Laboratory. Cytogenetic analysis was performed on phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband was ascertained to have additional material from chromosome 6p arising from complex chromosomal rearrangement in the father. Karyotyping is the basic, cost-effective preliminary investigation in a child with mental subnormality or congenital anomalies.

Cytogenetic profile of Indian patients with de novo myelodysplastic syndromes.

Background & objectives: Myelodysplastic syndrome (MDS) is a clonal haematopoietic stem cell disorder characterized by ineffective haematopoiesis and leukaemia progression. Cytogenetic analysis has proven to be a mandatory part of the diagnosis of MDS as well as a major indicator for predicting clinical course and outcome. Studies on cytogenetics of MDS are reported mostly from the West and only a few are available from Asian countries. We report herein cytogenetic studies on 40 Indian patients with primary MDS to find out the occurrence and type of chromosome abnormalities and recurring defects. Methods: Cytogenetic analysis was done using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). Results: Of the 40 patients, 19 patients (47.5%) showed clonal karyotypic abnormalities with distribution as follows: 3 of 15 (20%) of refractory anaemia (RA), 4 of 7 (57%) of refractory anaemia with excess blasts-1 (RAEB-1), 4 of 6 (67%) of refractory anaemia with excess blasts 2 (RAEB-2), 2 of 3 (67%) of refractory anaemia with ring sideroblasts (RARS), 2 of 4 (50%) of refractory cytopenia with multilineage dysplasia (RCMD), none (0%) RCMD-ringed sideroblasts (RCMD-RS) and 4 patients with 5q syndrome. The frequent abnormalities observed in our study were -7, 5q-and trisomy 8. Interpretation & conclusions: Two rare chromosomal abnormalities (6q-, 3q-) were found with unknown prognostic significance. Hence, cytogenetic analysis may be incorporated in the routine diagnosis of MDS since there are racial differences in clinical pictures and the molecular events.

Genome-wide scan of granular corneal dystrophy, type II: confirmation of chromosome 5q31 and identification of new co-segregated loci on chromosome 3q26.3

Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected novel nine candidate loci for CGD2. In simulation analysis, the only 3q26.3 region including neuroligin 1 gene (NLGN1) was supported by empirical statistic significance. To investigate the effect of genetic heterogeneity in linkage analysis, we classified CGD2 families into two subgroups. Although we could not find a significant evidence for correlation between the 3q26.3 region and CGD2 phenotypes, this first genome-wide analysis with CGD2 families in Korea has a very important value for offering insights in genetics of CGD2. In addition, the co-segregating loci with CGD2 including 3q26.3 would be a good target for further study to understand the pathophysiology of CGD2.

Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy

Genomic scan analyses have suggested that the chemokine receptor cluster [CCR2, CCR3, CCR5 <300 kb span] on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms [SNP] and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma [453 unrelated individuals] including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test [SPT 3 mm] to a panel of common inhaled allergens. From a panel often known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5delta32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene

Chromosome 3p alterations in northeastern Thai women with cervical carcinoma.

The purpose of this study was to determine the incidence of the loss of heterozygosity (LOH) among normal cervixes, cervical intraepithelial neoplasias (CINs) and invasive cervical cancers (ICCs). DNA samples (136) were obtained from 31 normal cervixes, 49 CINs and 56 ICCs. Four polymorphic microsatellite markers (D3S1300, D3S1351, D3S1478 and D3S4103) covering the chromosome 3p arm, were employed. LOH at one or more loci were identified in: 9/31 (8.1%) normal cervixes, 17/49 (14.6%) CINs and 26/56 (22.1%) invasive cancers. The incidence of the LOH at 3p varied for each locus and ranged from 5.6% for D3S1351 to the highest rate of 16.6% for D3S1300. We thus found that LOH of chromosome 3p can occur in normal cervixes and that incidences increase in CINs and ICCs. Deletion in the 3p14.2 (D3S1300) and 3p21.2 (D3S1478) regions might be an early event and, in fact, necessary for cervical cancer progression. The loss of function of tumor suppressor genes (TSGs) located in these regions may have a sequential effect in cervical cancer carcinogenesis.

Identificación de una nueva anomalía citogenética en el síndrome de duplicación 3q / Identification of a new cytogenetic rearrangement in the duplication 3q syndrome

Se presenta el caso de un paciente masculino con retraso psicomotor y características fenotípicas del síndrome dup (3q). El estudio citogenético reveló un rearreglo cromosómico de novo consistente en una inserción invertida de la región duplicada que resultó en un cariotipo 46,XY, der (3) (pter - q13.3::q27 - q26.1::q13.3 - qter). Esta aberración cromosómica no habria sido descrita previamente en este síndrome