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1.
Yi Chuan ; 43(1): 74-83, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33509776

RESUMO

Trisomy 18 syndrome is one of the most common autosomal aneuploidy disorders. Little is known about the genetic regulation leading to the clinical phenotypes associated with the occurrence and development of trisomy 18 syndrome disorders (e.g., mental retardation, cardiac and renal abnormalities). To explore the regulatory factors that influence the phenotypes of the disease, this study used single-cell ATAC sequencing to analyze transcription factors in the accessibility chromatin regions of the single-nucleus cells of the cord blood from 18-trisomy syndrome and control subjects. A single-cell library constructed by capturing 11,611 cells identified seven major immune cell populations, and the results of cell number statistics suggested the presence of abnormalities in the immune system of 18-trisomy syndrome patients. Fourteen transcription factors (P<0.05, |FC|>1.2) were identified by analyzed accessibility chromatin regions. The relative expression levels of four of these transcription factors (TEAD1, TEAD2, TEAD4, Twist2) were confirmed using real-time quantitative fluorescence PCR. In conjunction with information from the literature, this study suggests that these four transcription factors may be associated with abnormalities in cardiac and skeletal development in patients with the 18-trisomy syndrome, thereby providing candidate molecules for mechanistic studies on the occurrence and development of the 18-trisomy syndrome phenotypes.


Assuntos
Cromatina/genética , Fatores de Transcrição/genética , Síndrome da Trissomía do Cromossomo 18/genética , Cromossomos Humanos Par 18/genética , Proteínas de Ligação a DNA , Biblioteca Gênica , Humanos , Sistema Imunitário , Proteínas Musculares , Proteínas Nucleares , Proteínas Repressoras , Análise de Célula Única , Proteína 1 Relacionada a Twist
3.
Biomed Khim ; 66(6): 469-476, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33372905

RESUMO

Using electrospray ionization tandem mass spectrometry, a comparative analysis of the HaCaT keratinocyte proteins encoded by the 18th chromosome was performed before and after exposure to sodium dodecyl sulfate (25 mg/ml) and to Triton X-100 (12.5 mg/ml) in a subtoxic dose for 48 hours. Proteins were identified using the SearchGUI platform (X!Tandem and MS-GF+ search engines). In total, 1284 proteins were found in immortalized human HaCaT keratinocytes and about 75% of them were identified by two or more peptides. Were identified, that 26 proteins were encoded by genes of chromosome 18. Among these proteins, 17 were common for control cells and HaCaT cells treated with SDS. Proteins MARE2 and CTIF were identified only in control keratinocytes. Seven identified proteins encoded by genes of chromosome 18 were found only in detergent-treated keratinocytes: LMAN1, NDUV2, SPB3, VPS4B, KDSR, ROCK1 and RHG28.


Assuntos
Queratinócitos , Linhagem Celular , Cromossomos Humanos Par 18/genética , Detergentes/farmacologia , Humanos , Lectinas de Ligação a Manose , Proteínas de Membrana , Proteoma/genética , Dodecilsulfato de Sódio/farmacologia , Quinases Associadas a rho
4.
Ann Hematol ; 99(10): 2441-2443, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32808104
5.
Adv Exp Med Biol ; 1195: 163-166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468472

RESUMO

INTRODUCTION: Chromosome 18q deletion syndrome (18q-) is a rare chromosomal disorder with phenotypic variability, including mental deficiency, short stature, hypotonia, cleft palate, and hearing impairment. We present a case with features of 18q- syndrome who had combined 18q partial monosomy and 18p partial trisomy. MATERIAL AND METHODS: A 50-year-old female patient was examined during the genetic counseling of her brother. She had a history of congenital cleft palate and developmental deficiency with hypotonia, hearing loss, and epilepsy until adulthood. Her family history was free of related cases. Karyotype analysis and comparative genomic hybridization array (aCGH) were performed in patient's blood samples. RESULTS: Clinical examination showed features of 18q- syndrome including hypotonia and tremor. Neuropsychological deficiency of moderate cognitive disorder was noticed. The patient's karyotype was normal. The aCGH analysis revealed 8 Mb deletion (del18q22.3q23) and 7.2 Mb duplication (dup18p11.32p11.23). CONCLUSION: Almost all patients' clinical features were associated with 18q- syndrome. There are very few reported cases with similar genotype possibly caused by a de novo unequal recombination mechanism.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 18/genética , Anormalidades Craniofaciais/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Fenótipo , Síndrome
6.
Zhonghua Fu Chan Ke Za Zhi ; 55(2): 106-111, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32146739

RESUMO

Objective: To evaluate the efficacy of cell free DNA (cf-DNA) screening in prenatal care by analyzing the follow-up information and pregnancy outcomes. Methods: All cf-DNA cases conducted in Women's Hospital of Nanjing Medical University from August 2011 to December 2017 were enrolled. The general information of the pregnancies, cf-DNA results, confirmatory testing results, and the follow-up results were collected. The pregnancy outcomes were analyzed in cases with low risk cf-DNA results as well as with high risk results for common trisomies, which were trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). The sensitivity, specificity, positive predictive value and negative predictive value of cf-DNA screening were calculated. Results: (1) A total of 43 615 cf-DNA cases were involved, with 44 cases (0.10%, 44/43 615) test failure results, 314 cases (0.72%, 314/43 571) high risk results for common trisomies and 43 257 cases (99.27%, 43 257/43 571) low risk results. (2) Among 277 cases (88.21%, 277/314) high risk cases were successfully followed up, and 228 cases (82.31%, 228/277) underwent invasive confirmatory prenatal diagnosis. In the low risk results, 36 826 cases (85.13%, 36 826/43 257) were successfully followed up, and 572 (1.55%, 572/36 826) cases were found to have adverse pregnancy outcomes, among which 4 false negative cf-DNA results were confirmed. (3) In the 37 103 successfully followed up cf-DNA cases, the sensitivity for T21, T18, T13 were calculated as 97.96%, 96.67% and 100.00%, respectively; the specificity for T21, T18, T13 were calculated as 99.96%, 99.95% and 99.95%, respectively. The positive predictive value for T21, T18, T13 were calculated as 90.57%, 63.04% and 17.39%, respectively. The negative predictive value for T21, T18, T13 were calculated as 99.99%, 99.98% and 100.00%. Conclusions: Cf-DNA is effective in detecting common trisomies, with a high sensitivity and specificity. However, the follow-up information revealed several potential limitations in current clinical practice, such as a number of cases with high risk results rejected invasive confirmatory testing, as well as the genetic diagnostic results for most low risk cases with an adverse pregnancy outcome aren't obtained. Genetic counseling and the follow-up for all the cf-DNA cases should be emphasized in the future.


Assuntos
Ácidos Nucleicos Livres , Transtornos Cromossômicos/diagnóstico , Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 18/genética , Feminino , Seguimentos , Testes Genéticos/métodos , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Sensibilidade e Especificidade , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Ultrassonografia Pré-Natal
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 459-461, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219837

RESUMO

OBJECTIVE: To explore the genetic basis for a child featuring delayed intellectual development. METHODS: The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents. RESULTS: No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8. CONCLUSION: The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.


Assuntos
Variações do Número de Cópias de DNA , Hiperventilação/genética , Deficiência Intelectual/genética , Fator de Transcrição 4/genética , Criança , Deleção Cromossômica , Cromossomos Humanos Par 18/genética , Deficiências do Desenvolvimento/genética , Facies , Humanos , Fenótipo
8.
Int J Biol Macromol ; 147: 513-520, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31931065

RESUMO

The alternative splicing is a mechanism increasing the number of expressed proteins and a variety of these functions. We uncovered the protein domains most frequently lacked or occurred in the splice variants. Proteins presented by several isoforms participate in such processes as transcription regulation, immune response, etc. Our results displayed the association of alternative splicing with branched regulatory pathways. By considering the published data on the protein proteins encoded by the 18th human chromosome, we noted that alternative products display the differences in several functional features, such as phosphorylation, subcellular location, ligand specificity, protein-protein interactions, etc. The investigation of alternative variants referred to the protein kinase domain was performed by comparing the alternative sequences with 3D structures. It was shown that large enough insertions/deletions could be compatible with the kinase fold if they match between the conserved secondary structures. Using the 3D data on human proteins, we showed that conformational flexibility could accommodate fold alterations in splice variants. The investigations of structural and functional differences in splice isoforms are required to understand how to distinguish the isoforms expressed as functioning proteins from the non-realized transcripts. These studies allow filling the gap between genomic and proteomic data.


Assuntos
Processamento Alternativo , Cromossomos Humanos Par 18 , Bases de Dados de Proteínas , Proteínas de Ligação a RNA , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Humanos , Estrutura Secundária de Proteína , Proteômica , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
9.
Hum Mol Genet ; 29(2): 238-247, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31813999

RESUMO

Trisomy 18, sometimes called Edwards syndrome, occurs in about 1 in 6000 live births and causes multiple birth defects in affected infants. The extra copy of chromosome 18 causes the altered expression of many genes and leads to severe skeletal, cardiovascular and neurological systems malformations as well as other medical problems. Due to the low rate of survival and the massive genetic imbalance, little research has been aimed at understanding the molecular consequences of trisomy 18 or considering potential therapeutic approaches. Our research is the first study to characterize whole-genome expression in fibroblast cells obtained from two patients with trisomy 18 and two matched controls, with follow-up expression confirmation studies on six independent controls. We show a detailed analysis of the most highly dysregulated genes on chromosome 18 and those genome-wide. The identified effector genes and the dysregulated downstream pathways provide hints of possible genotype-phenotype relationships to some of the most common symptoms observed in trisomy 18. We also provide a possible explanation for the sex-specific differences in survival, a unique characteristic of trisomy 18. Our analysis of genome-wide expression data moves us closer to understanding the molecular consequences of the second most common human autosomal trisomy of infants who survive to term. These insights might also translate to the understanding of the etiology of associated birth defects and medical conditions among those with trisomy 18.


Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 18/genética , Fibroblastos/metabolismo , Regulação da Expressão Gênica/genética , Síndrome da Trissomía do Cromossomo 18/genética , Células Cultivadas , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genômica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , RNA-Seq , Síndrome da Trissomía do Cromossomo 18/etiologia , Síndrome da Trissomía do Cromossomo 18/patologia
10.
Int J Oncol ; 56(1): 7-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789408

RESUMO

Although the majority of patients with follicular lymphoma (FL) harbor the t(14;18)(q32;q21) IGH/BCL2 gene rearrangement that leads to the overexpression of BCL2 protein, approximately 20% of FL cases lack t(14;18)(q32;q21). It is considered that BCL2 overexpression underscores the development of the majority of cases of FL and their transformation to more aggressive lymphoma [known as transformed FL (tFL)]. However, FL cases lacking the t(14;18)(q32;q21) translocation exhibit symptoms analogous to their t(14;18)­positive counterparts. An important goal of recent research on FL has been to clarify the distinctions between the two different forms of FL. Numerous studies have shed light onto the genetic and molecular features of t(14;18)­negative FL and the related clinical manifestations. In this review, we summarize the current knowledge of t(14;18)­negative FL occurring in the lymph nodes with an emphasis on the underlying molecular and clinical features. In addition, novel treatment directions are discussed.


Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Linfoma Folicular/genética , Linfoma Folicular/patologia , Translocação Genética , Humanos , Prognóstico
11.
Photodermatol Photoimmunol Photomed ; 36(1): 29-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31374130

RESUMO

BACKGROUND: Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce. PURPOSE: To evaluate the characteristics of acquired EPP. METHODS: A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS). RESULTS: We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 µg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients. CONCLUSION: We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria.


Assuntos
Azacitidina/uso terapêutico , Síndromes Mielodisplásicas , Transtornos de Fotossensibilidade , Protoporfiria Eritropoética , beta Caroteno/uso terapêutico , Adulto , Idoso , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 18/metabolismo , Eritrócitos/metabolismo , Feminino , Ferroquelatase/genética , Ferroquelatase/metabolismo , Loci Gênicos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Transtornos de Fotossensibilidade/induzido quimicamente , Transtornos de Fotossensibilidade/tratamento farmacológico , Transtornos de Fotossensibilidade/genética , Transtornos de Fotossensibilidade/metabolismo , Protoporfiria Eritropoética/induzido quimicamente , Protoporfiria Eritropoética/tratamento farmacológico , Protoporfiria Eritropoética/genética , Protoporfiria Eritropoética/metabolismo , Protoporfirinas/genética , Protoporfirinas/metabolismo
12.
Arch Iran Med ; 22(10): 627-628, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31679365

RESUMO

Monosomy 18p syndrome is one of the prototypical examples of autosomal terminal deletions. This deletion can be the consequence of de novo deletions, malsegregation of a balanced parental translocation, cryptic subtelomeric deletions or ring chromosome 18. The present case is a rare cytogenetic variant of monosomy 18 as a consequence of whole-arm translocation between chromosomes 13 and 18 which has been reported only three times previously.


Assuntos
Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13 , Translocação Genética , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 18/genética , Análise Citogenética , Humanos , Lactente , Masculino , Cromossomos em Anel
13.
Taiwan J Obstet Gynecol ; 58(6): 798-800, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759530

RESUMO

OBJECTIVE: The aim of this study was to evaluate the usefulness of ultrasound in pregnancies with a positive non-invasive prenatal testing (NIPT) result for trisomy 18/13. MATERIALS AND METHODS: During a four-year period, the pregnant women who were referred for invasive genetic testing because of positive NIPT results for trisomy 18/13 were included in this study. An in-depth ultrasound was done for these patients before invasive procedures. The data of fetal ultrasound and cytogenetic results were collected. RESULTS: There were 81 patients with a positive NIPT result for trisomy 18/13, including 39 (30 positive for trisomy 18; 9 positive for trisomy 13) within 12-14 weeks of gestation, and 42 (31 positive for trisomy 18; 11 positive for trisomy 13) within 15-22 weeks. The PPV of NIPT was 60.7% for trisomy 18, and 30% for trisomy 13, respectively. When adding ultrasound to NIPT, the new PPV for trisomy 18 was 100%, and the negative predictive value (NPV) was 92.3%, with a NPV of 85.7% in the first trimester and a NPV of 100% in the second trimester, respectively. The new PPV and NPV for trisomy 13 were 100% and 100%, respectively. CONCLUSION: By adding ultrasound to the NIPT, we achieved much higher PPVs and NPVs for trisomy 18/13. A normal scan can help to alleviate stress in parents caused by false positive NIPT results.


Assuntos
Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Ultrassonografia Pré-Natal/métodos , Adulto , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , DNA/análise , Feminino , Seguimentos , Testes Genéticos/métodos , Idade Gestacional , Humanos , Recém-Nascido , Cariotipagem , Gravidez , Resultado da Gravidez , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(10): 1010-1014, 2019 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-31598948

RESUMO

OBJECTIVE: To explore the genetic basis for a child with developmental delay and congenital syndactyly. METHODS: G-banding chromosomal karyotyping and chromosomal microarray analysis (CMA) were performed on peripheral blood sample from the child. RESULTS: The child was ascertained as 46, XY, r(18)[52]/45,XY,?18[3]. A 18q21.32-q23 deletion was identified by CMA with a size of 19.85 Mb, which has encompassed 99 genes including CTDP1, TXNL4A, TSHZ1, PIGN, RTTN, TNFRSF11A, KDSR and CYB5A. CONCLUSION: Clinical phenotype of the patient with ring chromosome 18 is associated with the size of the euchromatin loss and involved genes. As a useful complement to conventional karyotyping, CMA has provided an powerful tool for delineating complex chromosomal aberrations.


Assuntos
Aberrações Cromossômicas , Deficiências do Desenvolvimento/genética , Sindactilia/genética , Criança , Cromossomos Humanos Par 18/genética , Citogenética , Humanos , Cariotipagem , Cromossomos em Anel
15.
Cytogenet Genome Res ; 159(2): 74-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31658462

RESUMO

We present a patient with a de novo derivative chromosome 18 which includes a terminal deletion of 18p and a terminal duplication of 18q accompanied by a cryptic duplication of 18p. The girl had mild dysmorphic features such as micro-retrognathia, upslanted palpebral fissures, bilateral epicanthus, high palate, low-set ears, short neck, and full cheeks. She also had an H-type tracheoesophageal fistula which required surgery. Her cognitive and motor skills were delayed. Karyotype analysis showed an additional segment on the short arm of chromosome 18. Chromosomal microarray revealed a 7.3-Mb terminal loss from 18p11.32 to 18p11.23, a 22.2-Mb terminal gain from 18q21.31 to 18q23, and a 3.9-Mb interstitial gain from 18p11.22 to 18p11.21. We hypothesize that the mother has gonadal mosaicism for normal chromosome 18, der(18)dup(p11.22p11.21), and der(18)dup(p11. 22p11.21)inv(18)(p11.22q21.31), or both the terminal del/dup and the interstitial duplication occurred simultaneously.


Assuntos
Cromossomos Humanos Par 18/genética , Deleção Cromossômica , Citogenética/métodos , Feminino , Humanos , Lactente , Cariotipagem/métodos
16.
Nat Commun ; 10(1): 4495, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582743

RESUMO

Aneuploidy is a major source of gene dosage imbalance due to copy number alterations (CNA), and viable human trisomies are model disorders of altered gene expression. We study gene and allele-specific expression (ASE) of 9668 single-cell fibroblasts from trisomy 21 (T21) discordant twins and from mosaic T21, T18, T13 and T8. We examine 928 single cells with deep scRNAseq. Expected and observed overexpression of trisomic genes in trisomic vs. diploid bulk RNAseq is not detectable in trisomic vs. diploid single cells. Instead, for trisomic genes with low-to-average expression, their altered gene dosage is mainly due to the higher fraction of trisomic cells simultaneously expressing these genes, in agreement with a stochastic 2-state burst-like model of transcription. These results, confirmed in a further analysis of 8740 single fibroblasts with shallow scRNAseq, suggest that the specific transcriptional profile of each gene contributes to the phenotypic variability of trisomies. We propose an improved model to understand the effects of CNA and, generally, of gene regulation on gene dosage imbalance.


Assuntos
Variações do Número de Cópias de DNA , Dosagem de Genes , Modelos Genéticos , Transcriptoma/genética , Trissomia/genética , Alelos , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 8/genética , Síndrome de Down/genética , Feminino , Fibroblastos , Perfilação da Expressão Gênica , Humanos , Masculino , Mosaicismo , Fenótipo , RNA-Seq , Análise de Célula Única
17.
Sci Rep ; 9(1): 12717, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481703

RESUMO

Recent studies imply that rare variants contribute to the risk of schizophrenia, however, the exact variants or genes responsible for this condition are largely unknown. In this study, we conducted whole genome sequencing (WGS) of 20 Chinese families. Each family consisted of at least two affected siblings diagnosed with schizophrenia and at least one unaffected sibling. We examined functional variants that were found in affected sibling(s) but not in unaffected sibling(s) within a family. Matching this criterion, a frameshift heterozygous deletion of CA (-/CA) at chromosome 18:24722722, also referred to as rs752084147, in the Carbohydrate Sulfotransferase 9 (CHST9) gene, was detected in two families. This deletion was confirmed by PCR-based Sanger sequencing. With the observed frequency of 0.00076 in Han Chinese population, we performed both case-control and family-based analyses to evaluate its association with schizophrenia. In the case-control analyses, Chi-square test P-value was 6.80e-12 and the P-value was 0.0008 after one million simulations. In family-based segregation analyses, segregation P-value was 7.72e-7 and simulated P-value was 5.70e-6. For both the case-control and family-based analyses, the CA deletion was significantly associated with schizophrenia in the Chinese population. Further investigation of this gene  is warranted in the development of schizophrenia by utilizing larger and more ethnically diverse samples.


Assuntos
Americanos Asiáticos/genética , Cromossomos Humanos Par 18/genética , Família , Mutação da Fase de Leitura , Polimorfismo de Nucleotídeo Único , Esquizofrenia , Sulfotransferases/genética , Feminino , Humanos , Masculino , Esquizofrenia/etnologia , Esquizofrenia/genética , Sequenciamento Completo do Genoma
18.
BMJ Case Rep ; 12(8)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31473642

RESUMO

We report two sisters with developmental delay and dysmorphic features, as well as a history of seizures. Both sisters have short stature, microcephaly and shared facial dysmorphisms. We detected an 18.1 Mb interstitial gain in 1q31.3q41 and a 140 kb interstitial loss in 7p11.2 in both siblings by using array analysis in the older sister and copy number variation analysis in whole exome sequencing data in the younger sister. We further examined parental chromosomes and found an insertional translocation in the unaffected father, having a 46,XY,ins(7;1)(p11.2;q31.3q41) karyotype. A 1.8 Mb loss at the rearranged 1q segment was subsequently detected on additional array analysis in the father, as well as the 140 kb loss in 7p11.2. We describe the clinical consequences of the 18.1 Mb duplication of the long arm of chromosome 1 due to an unbalanced paternal insertional translocation and compare these with the clinical phenotypes of patients with an overlapping 1q duplication.


Assuntos
Duplicação Cromossômica/genética , Cromossomos Humanos Par 18/genética , Deficiências do Desenvolvimento/genética , Herança Paterna/genética , Translocação Genética/genética , Criança , Feminino , Humanos , Convulsões/genética , Irmãos
19.
Taiwan J Obstet Gynecol ; 58(5): 704-708, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542097

RESUMO

OBJECTIVE: We present detection of de novo del(18)(q22.2) and a familial 15q13.2-q13.3 microduplication in a fetus with congenital heart defects (CHD). CASE REPORT: A 27-year-old, primigravid woman was referred for genetic counseling because of fetal CHD. Prenatal ultrasound at 17 weeks of gestation revealed pericardial effusion, cardiomegaly and a large ventricular septal defect. The pregnancy was subsequently terminated at 18 weeks of gestation, and a 192-g female fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed a karyotype of 46,XX,del(18)(q22.2). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of the placental tissue revealed a 2.08-Mb 15q13.2-q13.3 microduplication encompassing KLF13 and CHRNA7, and a 10.74-Mb 18q22.2-q23 deletion encompassing NFATC1. The phenotypically normal father carried the same 2.08-Mb 15q13.2-q13.3 microduplication. Polymorphic DNA marker analysis confirmed a paternal origin of the distal 18q deletion. CONCLUSION: Prenatal diagnosis of CHD should include a complete genetic study of the embryonic tissues, and the acquired information is useful for genetic counseling.


Assuntos
Transtornos Cromossômicos/diagnóstico , Doenças Fetais/diagnóstico , Cardiopatias Congênitas/diagnóstico , Deficiência Intelectual/diagnóstico , Diagnóstico Pré-Natal/métodos , Convulsões/diagnóstico , Aborto Induzido , Adulto , Deleção Cromossômica , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 18/genética , Hibridização Genômica Comparativa/métodos , Análise Citogenética , Feminino , Doenças Fetais/genética , Aconselhamento Genético , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/genética , Humanos , Deficiência Intelectual/embriologia , Deficiência Intelectual/genética , Cariotipagem , Gravidez , Convulsões/embriologia , Convulsões/genética , Ultrassonografia Pré-Natal
20.
Mol Genet Genomic Med ; 7(9): e896, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31390163

RESUMO

BACKGROUND: Since the establishment of chromosomal microarrays in clinical practice, many new microdeletion/microduplication syndromes have been identified, including 18q11.2 microdeletion. Chromosome 18q deletion syndrome is commonly classified into distal deletion and a much rarer proximal interstitial deletion spanning the 18q11.2-q21.1 region. METHODS: We report two new patients and review 27 additional cases in DECIPHER/ClinGen databases and four cases from the literature, with more proximal 18q deletions involving 18q11-q12 (band 1 only; 17.2-43.5 Mb position) deletion. RESULTS: Common presentations of 18q11-q12 deletions include developmental delay/intellectual disability (DD/ID) (82%); speech delay/autism/attention deficit and hyperactivity/other behavioral problems (30%); conotruncal heart defects (15%); and subtle/non-specific facial dysmorphism. The deletion in four out of five cases with cardiac defect was distal to GATA6, suggesting an alternative mechanism other than haploinsufficiency of GATA6 as an underlying cause of cardiac malformations. Precocious puberty with advanced skeletal age was first observed in one patient, suggesting a unique and expanded phenotype of proximal 18q deletion. When comparing genotype-phenotype correlations from the present study with previous reports, the critical regions for selected phenotypes of 18q11-q12 deletion syndrome could be narrowed down as follows: 38.8-43.5 Mb for moderate to severe DD/ID, 19.6-24.4 Mb and 26.9-28.6 Mb for conotruncal heart defect. CONCLUSION: The detailed clinical delineation of the proximal 18q deletions identified in this study should contribute to better understanding of the genotype-phenotype correlations and better long-term care of patients with this rare syndrome.


Assuntos
Anormalidades Múltiplas , Deleção Cromossômica , Cromossomos Humanos Par 18/genética , Bases de Dados Genéticas , Cardiopatias Congênitas , Deficiência Intelectual , Transtornos do Desenvolvimento da Linguagem , Transtornos Mentais , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Pré-Escolar , Feminino , Fator de Transcrição GATA6/genética , Haploinsuficiência , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Humanos , Lactente , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/patologia , Masculino , Transtornos Mentais/genética , Transtornos Mentais/patologia
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