OBJECTIVE: To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis. METHODS: Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out. RESULTS: The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome. CONCLUSION When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.
Chromosome Disorders ; Chromosomes, Human, Pair 15 ; Comparative Genomic Hybridization ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Mosaicism

OBJECTIVE: To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID). METHODS: Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA). RESULTS: Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance. CONCLUSION Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities/genetics* ; DNA Copy Number Variations ; Developmental Disabilities/genetics* ; Heart Defects, Congenital ; Humans ; Intellectual Disability/genetics*

As a male-specific chromosome, the structure of Y chromosome is complex and lacks of recombination, with numerous repeating, amplifying and palindromic sequences. The research of Y chromosome is difficult and slow since there are few protein coding genes and a large amount of heterochromatin which has caused extreme difficulty for sequencing. In recent years, an increasing number of studies have been focused on the Y chromosome. With the completion of the sequencing of human Y chromosome, the rapid development of sequencing technology, and the composition of DNA sequences in human Y chromosomes and the determination of gene content. This paper has summarized the structural composition and genes function of human Y chromosome, as well as the related hereditary diseases, with an aim to provide reference for Y chromosome-related genetic research.
Chromosomes, Human, Y/genetics* ; Humans ; Male

OBJECTIVE: To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS). METHODS: Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed. RESULTS: On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent. CONCLUSION SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.
Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; DNA Copy Number Variations ; Genetic Testing ; Humans ; Infant, Newborn ; Intellectual Disability/genetics* ; Male ; Phenotype ; Smith-Magenis Syndrome/genetics*

OBJECTIVE: Utilize high-resolution chromosome analysis and microarray detection to determine the genetic etiology of infertility of a 32-year old female patient. METHODS: The peripheral blood of the patient was cultured for high-resolution chromosome G and C banding karyotype analysis, and then 750K SNP-Array chip detection was performed. RESULTS: Karyotype analysis results showed that the patient's karyotype was 45,XX,-13 [7]/46,XX,r(13) (p13q34) [185]/46,XX,dic r(13;13)(p13q34;p13q34) [14]/ 47,XX,+der(13;13;13;13) (p13q34;p13q34;p13q34; p13q34), dic r(13;13) [1]/ 46,XX [3]. The microarray results showed that the patient had a 3.3 Mb deletion in the 13q34 segment of chromosome 13, which may be related to infertility. CONCLUSION Infertility of the patient reported in this article may be related to the deletion of chromosome segment (13q34-qter).
Adult ; Chimera ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Dacarbazine ; Female ; Humans ; Infertility/genetics* ; Ring Chromosomes

Multiple myeloma (MM) is a kind of hematologic malignancy occurring in plasma cells. Cytogenetic technique plays an important role in risk stratification of MM. 1q21 amplification is one of the common chromosomal abnormalities in MM. Studies have shown that 1q21 amplification is associated with poor prognosis in MM patients. At present, with the development of new drugs, cellular immunotherapy, and improvement of hematopoietic stem cell transplantation technology, the remission depth and survival time of MM significantly increased. Rapid and accurate identification of high-risk patients and individualized treatment according to the patient's condition is the key to improve the therapeutic effect of MM. This article reviews the mechanism of 1q21 amplification in MM and the efficacy of new drugs in the treatment of MM with 1q21 chromosome amplification.
Chromosome Aberrations ; Chromosomes ; Chromosomes, Human, Pair 1/genetics* ; Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Myeloma/drug therapy* ; Prognosis

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary , the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.
Aneuploidy ; Female ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis/methods* ; Sex Chromosome Aberrations ; Sex Chromosomes/genetics*

Objective: To investigate the clinical and genetic characteristics of epilepsy associated with chromosome 16p11.2 microdeletion. Methods: The patients (n=10) with 16p11.2 microdeletion found in children with epilepsy treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2018 to January 2021 were collected. The clinical manifestations, gene variations and prognosis were analyzed retrospectively. Results: A total of 10 children's data were collected, including 5 male and 5 female. The onset age of epilepsy was 4.5 (4.1,5.0) months. Regarding the seizure types, 7 cases had focal seizures with secondary generalization, 2 cases had generalized seizures, and 1 case had tonic seizures and spasms. Nine cases had cluster seizure attacks and 3 cases had status epilepticus. Seven cases had focal or multifocal epileptiform discharges in interictal electroencephalogram (EEG), 3 cases had borderline or normal EEG. Brain magnetic resonance imaging showed polymicrogyria in 1 case, paraventricular leukomalacia in 1 case, delayed myelination of white matter in 3 cases, and no obvious abnormalities in the other 5 cases. The patients were followed up for 0.5-3.5 years, with 1-3 kinds of antiepileptic drugs taken orally. The case with polymicrogyria still had seizures, however the other 9 cases had seizures controlled. The age of the last seizure attack was 8 (6, 12) months. There were 6 cases with mental and motor developmental delay before epilepsy onset. During the follow-up, 7 cases were retarded to varying degrees, while 3 cases had normal development. Regarding the genetic detection methods, 7 cases underwent whole exome sequencing, 2 cases underwent whole genome copy number variation detection, and 1 case underwent whole genome sequencing. The length of the 16p11.2 deletion in 10 cases ranged from 525 to 951 kb, and all contained the PRRT2 gene intact. Six cases were de novo variants, 1 case was inherited from the mother who had a history of convulsions in early childhood, and the source of variant was not verified in 3 cases, none of whose parents had relevant phenotype. Conclusions: The epilepsy associated with 16p11.2 microdeletion is mainly induced by the heterozygous deletion of PRRT2 gene in this region, however the phenotype is usually severe, and often combined with developmental and epileptic encephalopathy. Detection of copy number variation should be emphasized in children whose etiology is considered genetic but second-generation sequencing result is negative.
Child, Preschool ; Chromosomes ; DNA Copy Number Variations ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Male ; Polymicrogyria/genetics* ; Retrospective Studies ; Seizures/genetics*

OBJECTIVE: To report on a case of Smith-Magenis syndrome (SMS) due to a rare small-scale deletion. METHODS: Muscle samples from the the third fetus was collected after the in Medical history and clinical data of the patient were collected. The child and his parents were subjected to chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and copy number variation sequencing (CNV-seq). RESULTS: The child was found to have a normal karyotype. MLPA and CNV-seq detection showed that he has harbored a 1.22 Mb deletion and a 0.3 Mb duplication in the 17p11.2 region. Neither of his parents was found to have similar deletion or duplication. CONCLUSION The child was diagnosed with SMS due to a rare 1.22 Mb deletion in the 17p11.2 region, which is among the smallest deletions associated with this syndrome.
Abnormalities, Multiple/genetics* ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; DNA Copy Number Variations ; Humans ; Intellectual Disability/genetics* ; Male ; Smith-Magenis Syndrome/genetics*