We present clinical and cytogenetic data on 2 cases of partial trisomy 4p and partial trisomy 14q. Both patients had an extra der(14)t(4;14)(p15.31;q12) chromosome due to a 3:1 segregation from a balanced translocation carrier mother. Array analyses indicated that their chromosomal breakpoints were similar, but there was no relationship between the 2 families. Both patients showed prominent growth retardation and psychomotor developmental delay. Other phenotypic manifestations were generally mild and variable; for example, patient 1 had a short palpebral fissure and low-set ears whereas patient 2 had a round face, asymmetric eyes, small ears, a short neck, finger/toe abnormalities, and behavioral problems.
Abnormalities, Multiple/*genetics ; Child ; Child, Preschool ; *Chromosomes, Human, Pair 14 ; *Chromosomes, Human, Pair 4 ; Female ; Humans ; Karyotyping ; Translocation, Genetic ; *Trisomy

OBJECTIVE: To identify the Epstein-Barr virus (EBV) chromosomal integration sites in Raji cells. METHODS: EBV DNA was detected by Southern hybridization, and the viral chromosomal integration sites were identified using G banding and fluorescence in situ hybridization (FISH). RESULTS: BamHI-digested genomic DNA from Raji cells was hybridized with (32)P-labeled probe-1 (EBV genome 13,232 approximately 16,189) and Probe-2 (EBV genome 5 approximately 3,271), which generated 4 and 10, 23 kb positive bands respectively. The viral integration sites included 1p, 1q, 2q, 3p, 3q, 4 q, 5q, 6q, 7p, 7q, 9q,11p, 14 q, and 15q,and chromosomal bands 4 q, 2q, 1q and 7q were viral integration sites with high frequencies. Among the 33 signals counted, 7, 4, 4,and 4 signals were at the site 4 q, 2q, 1q, and 7q respectively, and 64% of the total signals were found in these 4 chromosomal bands. No viral integration occurred in chromosomes 16 approximately 22 or the sex chromosomes (X, Y). CONCLUSION This study firstly identifies the EBV integration sites in Raji cells using G banding and FISH. There are some viral integration sites with high frequencies in Raji cells, and EBV integrates into Raji cell genomes non-randomly.
Burkitt Lymphoma ; genetics ; pathology ; virology ; Cell Line, Tumor ; Chromosomes, Human, Pair 1 ; virology ; Chromosomes, Human, Pair 2 ; virology ; Chromosomes, Human, Pair 4 ; virology ; DNA, Viral ; genetics ; Genome, Viral ; Herpesvirus 4, Human ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Virus Integration ; genetics

OBJECTIVEComprehensive use of molecular cytogenetic techniques for the detection of 1 case of small chromosome translocation.

METHODSFollowing conventional chromosome preparation, G-banding karyotype analysis, spectral karyotyping (SKY), whole chromosome painting, two-color fluorescence in situ hybridization (FISH) and subtelomeric probe FISH were performed.

RESULTSG-banded karyotype was 46, XX, ?(22q11.3), SKY karyotype analysis was 46, XX, der (4)t(4;6) and found no abnormalities on chromosome 22, staining signal was not found with any abnormalities on chromosome 6. Two-color FISH indicated a chromosomal translocation segment of 22q13.3 to one end of the short arm of chromosome 4. Subtelomeric FISH probe showed the end of the long arm of chromosome 22 and the end of the short arm of chromosome 4 reciprocal translocation. High resolution G-banding and FISH result indicated 46, XX, t(4;22)(p15.3;q13.2).

CONCLUSIONThe testing of small chromosomal translocation should be combined with clinical information and integrated use of molecular cytogenetic techniques to improve the accuracy of diagnosis of chromosomal diseases.

Adult ; Chromosome Banding ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Spectral Karyotyping ; Translocation, Genetic ; genetics

OBJECTIVE: To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy. METHODS: Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration. RESULTS: Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q. CONCLUSION The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.
Chromosomes, Human, Pair 4 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic ; Wolf-Hirschhorn Syndrome ; genetics

OBJECTIVETo characterize the profile of chromosomal imbalances of esophageal squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan province.

METHODSComparative genomic hybridization (CGH) was used to examine 52 cases of primary SCC of esophagus.

RESULTSGains in part or in whole of chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q were all significantly correlated with pathologic staging (P < 0.05). Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P < 0.05).

CONCLUSIONThese observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and 20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC-related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q are the genetic aberrations critical for the development of esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are considered later events associated with tumor progression and are thought to confer metastatic potential to esophageal carcinoma. Furthermore, nodal and distant organ metastases involve different genes.

Carcinoma, Squamous Cell ; genetics ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Esophageal Neoplasms ; genetics ; Gene Amplification ; Humans ; Lymphatic Metastasis ; Neoplasm Metastasis ; genetics ; Neoplasm Staging ; Nucleic Acid Hybridization

Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2]]. FISH study showed the deletion of the 4p subtelomeric region with the intact 4q subtelomeric and WHS region. Both paternal and maternal karyotypes were normal. We compared the phenotypic variation with the previously reported cases of ring chromosome 4. The ring chromosome 4 with the subtelomeric deletion of short arm seems to be related with the phenotype of short stature.
*Chromosome Deletion ; *Chromosomes, Human, Pair 4 ; Growth Disorders/*diagnosis/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; *Ring Chromosomes ; Telomere

A 10-month-old boy suspected of genetic abnormality was admitted for fever and coughing. Routine G-banding chromosome analysis of the peripheral blood lymphocytes and hereditary pattern analysis on the basis of the karyotypes and disease history revealed that the karyotype of the boy's mother was 46, XX,t(4;9)(q31;p24), and that of the boy was XY,der(9)t(4;9)(q31;p24)mat. The mother was identified as a carrier of balanced translocation of the chromosome who gave the abnormal chromosome 9 to her son, and she had only a chance of 1:18 to have a normal offspring. This case reiterates the importance of antemarital examination and prenatal diagnosis for preventing chromosomal diseases.
Abnormalities, Multiple ; diagnosis ; Cerebral Palsy ; diagnosis ; Chromosome Disorders ; diagnosis ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 9 ; Humans ; Infant ; Male ; Translocation, Genetic ; genetics

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.
Chromosome Aberrations ; Chromosome Duplication ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Female ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Pedigree ; Phenotype

OBJECTIVETo search the susceptibility genes of gallstone disease in Chinese population.

METHODSA genome wide scan was performed in twelve families with gallstone disease using fluorescence-labeled microsatellite markers. Genehunter and Batchlink of Linkage package were used for non- parameter and parameter linkage analysis to search the linkage loci on chromosomes.

RESULTSFour loci of D3S1266, D4S406, D9S1682 and D11S902 showed suggestive evidence for linkage. nonparametric linkage analysis (NPL)-score of D4S406 and D9S1682 was 1.77 (P = 0.05) and 1.92 (P = 0.04) respectively. The corresponding logarithm of the odds ratio (LOD)-score of D3S1266, D9S1682 were 1.35 and 2.07, and showed a rise of LOD-score from 1.35 to 2.71, 2.07 to 2.40 respectively when families with later-found patients or with higher triglyceride level were analyzed alone. Transmitted disequilibrium test of D11S902 showed a P-value of 0.0027.

CONCLUSIONSChromosome 3, 4, 9 and 11 may contain genes involved in gallstone disease in Chinese population, and chromosome 3, 9 may hide genes that are liked to gallstone disease in families with later-found patients or with higher triglyceride concentration.

Age Factors ; Asian Continental Ancestry Group ; Body Mass Index ; Cholecystolithiasis ; ethnology ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Female ; Genetic Linkage ; Genetic Predisposition to Disease ; Humans ; Male ; Microsatellite Repeats ; Pedigree

Jarcho-Levin syndrome (JLS) is a condition manifested by malformations of vertebral bodes and related ribs. There are two major subtypes spondylocostal dysostosis and spondylothoracic dysostosis, with different survival rates, associated malformations, and inheritance patterns. We have experienced an autopsy case of a premature female fetus with multiple congenital anomalies. She was 30 weeks of gestational age, born as the second baby of twins and expired shortly after birth. A post-mortem examination revealed multiple abnormalities including cervicothoracic hemivertebrae, a diminished number of right-sided ribs, and pulmonary hypoplasia with left diaphragmatic hernia. In addition, there were anomalous rotation of the foregut, unfused pancreas and anomalous drainage of the superior vena cava. Chromosomal analysis showed 46, XX, del(4)(q ter).
Abnormalities, Multiple/genetics/*pathology ; Autopsy ; Chromosome Deletion ; Chromosomes, Human, Pair 4 ; Female ; Humans ; Infant, Newborn ; Ribs/*abnormalities ; Spine/*abnormalities ; Syndrome