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1.
Medicine (Baltimore) ; 100(10): e24010, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725812

RESUMO

RATIONALE: Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells. PATIENT SYMPTOMS: Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 µmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications. DIAGNOSES: Both patients were diagnosed with renal tumors with unknown pathology. INTERVENTIONS: Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma. OUTCOMES: Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable. LESSONS: Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Renais/diagnóstico , Linfoma/patologia , Neoplasias Retroperitoneais/patologia , Duplicação Cromossômica , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/urina , Esôfago/diagnóstico por imagem , Humanos , Hibridização in Situ Fluorescente , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Renais/genética , Neoplasias Renais/secundário , Neoplasias Renais/urina , Biópsia Líquida/métodos , Linfonodos/diagnóstico por imagem , Linfoma/genética , Linfoma/urina , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/genética , Neoplasias Retroperitoneais/urina , Espaço Retroperitoneal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Urinálise/métodos
2.
Artigo em Inglês | MEDLINE | ID: mdl-33321999

RESUMO

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.


Assuntos
Variações do Número de Cópias de DNA , Transtornos Mentais/genética , Transtornos do Neurodesenvolvimento/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Heterozigoto , Humanos
3.
Medicine (Baltimore) ; 99(40): e22532, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019458

RESUMO

RATIONALE: Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes, which can be detected in patients with developmental retardation, infertile problems, and prenatal fetus. We report 3 adult female with fertility problems carrying sSMC(14/22) and aim to explore the correlation between sSMC(14/22) and fertility problems in women. PATIENT CONCERNS: Three Chinese female patients were referred for infertility consultation in our hospital. DIAGNOSES: The karyotype of these 3 patients were 47, XX, +mar. The chromosome microarray analysis (CMA) detected various chromosomal duplications and deletions in the 3 cases: a 0.49Mb gain of 5q32 for case 1; a 0.54Mb gain of 14q32.33 and a 1.83Mb gain of 16p11.2 for case 2; a 0.37Mb loss of 13q21.2q21.31 and a 0.12Mb gain of Xp11.2 for case 3. Fluorescence in situ hybridization (FISH) using the specific probes for chromosomes 13/21, 14/22, and 15 was applied to identify the origination of these sSMC, which were all finally identified as sSMC(14/22). INTERVENTIONS: Case 1 underwent the artificial reproductive technology to get her offspring and finally delivered a healthy male infant at 39 weeks. Case 2 did not plan to choose in vitro fertilization (IVF) to get offspring. Case 3 refused to do assisted reproductive technology. OUTCOMES: The genotype-phenotype correlation of sSMC(14/22) remain unclear. However, the existence of sSMC(14/22) might negatively affect the fertility ability in sSMC female carriers. LESSONS: The combined application of traditional banding technique and molecular cytogenetic techniques can better identify more details of sSMC. For sSMC carriers with fertility problems, they could get their offsprings through assisted reproductive technologies after comprehensive fertility assessment.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 22/genética , Infertilidade Feminina/genética , Adulto , China , Duplicação Cromossômica , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariótipo
4.
Medicine (Baltimore) ; 99(42): e22533, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080687

RESUMO

RATIONALE: Split-hand/split-foot malformation (SHFM), also known as ectrodactyly, is a congenital limb malformation affecting the central rays of the autopod extending to syndactyly, median clefts of the hands and feet, aplasia/hypoplasia of phalanges, metacarpals and metatarsals. Duplication of this 10q24 region is associated with SHFM3. While the clinical and genetic heterogeneity of SHFM makes the prenatal diagnosis and genetic counseling more challenging and difficult. PATIENT CONCERNS: A physically normal pregnant woman had a systemic ultrasound at the second trimester, only identified the deformity of both hands and feet on the fetus. DIAGNOSES: The fetus was diagnosed as sporadic SHFM3. INTERVENTIONS: After seeking advice from genetic counseling, she decided to terminate the pregnancy. The induction of infant was done after appearance of bipedal clefts, lobster-claw appearance and partial loss of phalanges and metacarpals, leaving behind 2nd finger in the left hand and the 5th in the right hand. Furthermore, collection of umbilical cord is recommended to this fetus for genome-wide detection. OUTCOMES: An outcome of the gene detection from abortion shows that there is variation in copy number in genome of chromosome 1 and chromosome 10. LESSONS: This case study confirms an association between SHFM3 and chromosomal micro-duplication on 10q24.3, and the extension of clinical spectrum of SHFM3. It also proposes some prenatal diagnosis and genetic counseling to help in planning and management in affected pregnancy. This will reduce the congenital and development abnormalities in birth rate, as well as relive the economic, psychological, and physical burden to the affected families.


Assuntos
Aconselhamento Genético , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Diagnóstico Pré-Natal , Aborto Induzido , Duplicação Cromossômica , Feminino , Humanos , Gravidez
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(9): 953-957, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-32820506

RESUMO

OBJECTIVE: To detect genomic copy number variations (CNVs) among 145 children with unexplained mental retardation/developmental delay (MR/DD) by using low-depth whole-genome copy number variation sequencing (CNV-seq). METHODS: Peripheral blood samples were collected from the patients and subjected to DNA extraction and CNV-seq. The results were analyzed by a combination of bioinformatic tools. RESULTS: Forty-nine patients were found to carry a total of 67 CNVs with an average size of 5.27 Mb. Among these, 22 patients were assessed to carry MR/DD-related CNVs involving 21 syndromes. This gave a diagnostic rate of 15.17%(22/145) for CNVs associated with unexplained MR/DD. The corresponding regions of the 22 MR/DD-related CNVs in the human genome covered 174 MR/DD-related pathogenic genes, which have mapped to 18 sections on 10 chromosomes. CONCLUSION: Genomic CNVs-related microdeletions/duplications account for a significant proportion of unexplained MR/DD, for which CNV-seq can provide an accurate diagnosis.


Assuntos
Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento , Deficiência Intelectual , Sequenciamento Completo do Genoma , Criança , Deleção Cromossômica , Duplicação Cromossômica , Deficiências do Desenvolvimento/genética , Genômica , Humanos , Deficiência Intelectual/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 859-862, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761595

RESUMO

OBJECTIVE: To explore the clinical phenotype and genetic diagnosis of a patient featuring secondary amenorrhea, breast dysplasia and mental retardation. METHODS: Peripheral venous blood samples were collected from the patient and her family members and subjected to G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. RESULTS: The patient was found to have a karyotype of 46,X,der(X)(12qter→ 12q22::Xq23→ Xpter)mat, her mother had a karyotype of 46,X,t(X;12)(Xpter→ Xq23::12q22→ 12qter;12pter→ 12q22::Xq23→ Xqter), while her father and brother were both 46,XY. SNP-array analysis suggested the patient to be arr[hg19]12q22q24.33(94 792 972-133 777 562)× 3, Xq23q28(108 786 070-155 233 098)×1. CONCLUSION: The abnormal phenotypes of the patient can probably be attributed to the presence of Xq23-qter deletion and 12q22-qter duplication, both have derived from her mother's balanced t (X;12) translocation.


Assuntos
Deleção Cromossômica , Duplicação Cromossômica , Testes Genéticos , Translocação Genética , Bandeamento Cromossômico , Cromossomos Humanos Par 12 , Cromossomos Humanos X , Feminino , Humanos , Cariotipagem , Mães , Fenótipo
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 863-866, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761596

RESUMO

OBJECTIVE: To provide prenatal diagnosis for a pregnant women carrying a chromosome translocations using single nucleotide polymorphism array (SNP-array). METHODS: The fetus and its parents were subjected to chromosome karyotyping and SNP array analysis. RESULTS: A Xp22.12 microduplication was identified in the fetus with a size of 496.3 kb. Search of literature and database indicated the microduplication to be variant of unclear significance. The phenotypically normal mother has carried a 505.8 kb duplication at the same position. The father was normal for the testing. The couple decided to continue with the pregnancy and gave birth to a healthy girl at full-term. No abnormality was found during the follow-up. CONCLUSION: The Xp22.12 microduplication encompassed part of RPS6KA3 gene, which shows various features of Coffin-Lowry syndrome. Female with Xp22.12 microduplications may be asymptomatic carriers due to X chromosome inactivation. Our case may provide data for delineating the phenotype-genotype correlation of Xp22.12 microduplication.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos X , Diagnóstico Pré-Natal , Feminino , Feto , Testes Genéticos , Humanos , Cariotipagem , Polimorfismo de Nucleotídeo Único , Gravidez
8.
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
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(5): 555-558, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32335885

RESUMO

OBJECTIVE: To explore the genetic basis for an infant with multiple malformations including congenital heart disease and cleft palate. METHODS: The child and his parents were subjected to conventional chromosomal karyotyping and low-coverage massively parallel copy number variation sequencing (CNV-seq) analysis. RESULTS: The infant was found to have a 46,X,add(Y)(q11.23) karyotype, and his CNV-seq result was seq [hg19] 22q12.1q13.3 (29 520 001-51 180 000)× 3. His parents were found to be normal by both methods. CONCLUSION: The additional chromosomal material found on Yq, verified as duplication of 22q12.1-q13.3, may account for the abnormal phenotype in this infant. CNV-seq has provided a useful complement for the diagnosis and more accurate information for genetic counseling.


Assuntos
Anormalidades Múltiplas , Duplicação Cromossômica , Cromossomos Humanos Par 22 , Anormalidades Múltiplas/genética , Criança , Cromossomos Humanos Par 22/genética , Fissura Palatina/genética , Variações do Número de Cópias de DNA , Testes Genéticos , Cardiopatias Congênitas/genética , Humanos , Lactente , Cariotipagem
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 467-470, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219839

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with split hand/foot malformation (SHFM). METHODS: Genomic DNA of the proband and other affected members was extracted from peripheral blood samples. Chromosomal microarray analysis was employed to detect genome-wide copy number variations (CNVs). RESULTS: A 400 kb microduplication was identified in the 10q24.31-q24.32 region among all affected individuals. The microduplication has involved four genes, namely LBX1, BTRC, POLL and DPCD, in addition with part of FBXW4 gene. CONCLUSION: The 10q24.31-q24.32 microduplication has segregated with the disease phenotype in this pedigree and probably underlay the SHFM malformation in the patients.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 10/genética , Deformidades Congênitas do Pé , Deformidades Congênitas da Mão , Deformidades Congênitas dos Membros/genética , Grupo com Ancestrais do Continente Asiático , Variações do Número de Cópias de DNA , Deformidades Congênitas do Pé/genética , Testes Genéticos , Deformidades Congênitas da Mão/genética , Humanos , Linhagem
11.
BMJ Case Rep ; 13(3)2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32152069

RESUMO

​The advance in the human genetic field has permitted to identify small chromosome alterations and associate them to a specific phenotype. However, there are many mutations that have not yet been described in the literature. We describe the clinical case of a term newborn with appropriate weight to its gestational age, without perinatal background of interest that, at birth, presented: macrocephaly, hypertelorism, low-set ears, prominent forehead, micrognathia, camptodactyly, bilateral cryptorchidism, inspiratory stridor with the cry, multifocal systolic murmur, wide anterior fontanel and hypotonia of mixed characteristics and in whom a deletion of the 1q44 cytoband and a pathogenic duplication in the 9q32q34.3 cytoband were detected. We perform a review of the literature.


Assuntos
Anormalidades Múltiplas/genética , Duplicação Cromossômica , Fenótipo , Deleção de Sequência , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 9 , Técnicas de Genotipagem , Humanos , Recém-Nascido , Masculino
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 52-56, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922597

RESUMO

OBJECTIVE: To delineate the clinical features,inheritance pattern, and genotype-phenotype correlation of a Chinese patient with a 17q25.3 duplication. METHODS: Whole exome sequencing(WES), chromosomal microarray analysis (CMA), chromosomal karyotyping and fluorescence in situ hybridization (FISH) were employed for the analysis of the proband and his family members. RESULTS: A 5.7 Mb duplication at 17q25.3→qter was identified by WES and CMA in the 4-year-old boy with multiple congenital anomalies, which was classified as a clinically pathogenic variant. This duplication was confirmed by FISH, and was inherited from his unaffected mother who carried a balanced translocation. Further study revealed that his grandmother also carried the balanced translocation but had gestated three healthy children and had no abortion history. His uncle also carried the balanced translocation, while his aunt was normal. CONCLUSION: Above results have enriched the clinical phenotypes of 17q25.3 duplication. Genetic counseling was provided for the family. P4HB, ACTG1, BAIAP2 and TBCD genes may underlie the clinical features for the 17q25.3 duplication.


Assuntos
Anormalidades Múltiplas , Duplicação Cromossômica , Cromossomos Humanos Par 17 , Deficiências do Desenvolvimento , Anormalidades Múltiplas/genética , Adulto , Pré-Escolar , China , Cromossomos Humanos Par 17/genética , Deficiências do Desenvolvimento/genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Proteínas Associadas aos Microtúbulos , Translocação Genética
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 64-66, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-31922600

RESUMO

OBJECTIVE: To explore the genetic basis of a child with developmental delay and intellectual disability. METHODS: Peripheral blood samples of the child and his parents were collected for routine G-band karyotyping analysis and single nucleotide polymorphism array (SNP array) assay. Amniotic fluid sample was collected during the next pregnancy for prenatal diagnosis. RESULTS: No karyotypic abnormality was found in the child and his parents. SNP array showed that the child has carried a 855.3 kb microduplication in 15q11.2. His mother carried the same duplication but had no phenotypic anomaly. No microdeletion/microduplication was found in his father. Upon prenatal diagnosis, no abnormalities was found with the chromosomal karyotype and SNP array result of the fetus. CONCLUSION: 15q11.2 microduplication may result in developmental delay and intellectual disability, for which CYFIP1 may be a candidate gene. However, the duplication may increase the risk but with a low penetrance. This should attract attention during clinical consultation.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 15 , Deficiência Intelectual , Proteínas Adaptadoras de Transdução de Sinal , Criança , Bandeamento Cromossômico , Cromossomos Humanos Par 15/genética , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-Natal
14.
Autism Res ; 13(2): 187-198, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724820

RESUMO

16p11.2 copy-number variation (CNV) is implicated in neurodevelopmental disorders, with the duplication and deletion associated with autism spectrum disorder (ASD) and the duplication associated with schizophrenia (SCZ). The 16p11.2 CNV may therefore provide insight into the relationship between ASD and SCZ, distinct disorders that co-occur at an elevated rate, and are difficult to distinguish from each other and from common co-occurring diagnoses such as obsessive compulsive disorder (OCD), itself a potential risk factor for SCZ. As psychotic symptoms are core to SCZ but distinct from ASD, we sought to examine their predictors in a population (n = 546) of 16p11.2 CNV carriers and their noncarrier siblings recruited by the Simons Variation in Individuals Project. We hypothesized that psychotic symptoms would be most common in duplication carriers followed by deletion carriers and noncarriers, that an ASD diagnosis would predict psychotic symptoms among CNV carriers, and that OCD symptoms would predict psychotic symptoms among all participants. Using data collected across multiple measures, we identified 19 participants with psychotic symptoms. Logistic regression models adjusting for biological sex, age, and IQ found that 16p11.2 duplication and ASD diagnosis predicted psychotic symptom presence. Our findings suggest that the association between 16p11.2 duplication and psychotic symptoms is independent of ASD diagnosis and that ASD diagnosis and psychotic symptoms may be associated in 16p11.2 CNV carriers. Autism Res 2020, 13: 187-198. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Either deletion or duplication at chromosome 16p11.2 raises the risk of autism spectrum disorder, and duplication, but not deletion, has been reported in schizophrenia (SCZ). In a sample of 16p11.2 deletion and duplication carriers, we found that having the duplication or having an autism diagnosis may increase the risk of psychosis, a key feature of SCZ.


Assuntos
Transtorno do Espectro Autista/genética , Cromossomos Humanos Par 16/genética , Variações do Número de Cópias de DNA/genética , Transtornos Psicóticos/genética , Esquizofrenia/epidemiologia , Adolescente , Adulto , Deleção Cromossômica , Duplicação Cromossômica/genética , Feminino , Humanos , Masculino , Adulto Jovem
16.
Eur J Med Genet ; 63(4): 103774, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31585183

RESUMO

We present the case of a male infant with bilateral perisylvian polymicrogyria associated with a de novo duplication of chromosome region 17p13.3p13.2. To our knowledge, this is the first report of polymicrogyria associated with the 17p13.3 contiguous gene duplication syndrome. Testing for known monogenic causes of polymicrogyria was negative and there was no clinical evidence of an acquired prenatal cause. Given the critical, dose-sensitive role that the 17p13.3 region plays in brain development, we suggest that the chromosome duplication is the most likely explanation for the polymicrogyria. Clinical and functional studies have demonstrated deleterious effects of increased LIS1 expression on the developing brain and the contribution of YWHAE to the brain phenotype of the 17p13 duplication syndrome. There is also evidence that CRK, the other candidate gene in this region, via interaction with LIS1, plays a critical role in cortical development. In addition to LIS1, YWHAE and CRK, our patient's chromosome duplication involves at least 100 other genes, less than half of which are annotated at the time of writing. It is expected that the ongoing use of chromosome microarray and next-generation sequencing to investigate the genetic causes of brain malformations will continue to extend our understanding of the 17p13 region and of the contributions of the genes in this region to cortical development.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos Par 17/genética , Polimicrogiria/genética , Polimicrogiria/patologia , Humanos , Lactente , Masculino , Fenótipo
17.
Nucleic Acids Res ; 48(1): 130-140, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31713617

RESUMO

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.


Assuntos
Doença de Charcot-Marie-Tooth/terapia , Terapia de Alvo Molecular/métodos , Proteínas da Mielina/genética , Bainha de Mielina/metabolismo , Células de Schwann/metabolismo , TATA Box , Animais , Axônios , Sistemas CRISPR-Cas , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Duplicação Cromossômica , Cromossomos Humanos Par 17 , Modelos Animais de Doenças , Edição de Genes/métodos , Humanos , Injeções , Camundongos , Proteínas da Mielina/metabolismo , Bainha de Mielina/patologia , Cultura Primária de Células , Regiões Promotoras Genéticas , Células de Schwann/patologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
19.
G3 (Bethesda) ; 10(1): 37-42, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31712258

RESUMO

Different Musa species, subspecies, and cultivars are currently investigated to reveal their genomic diversity. Here, we compare the genome sequence of one of the commercially most important cultivars, Musa acuminata Dwarf Cavendish, against the Pahang reference genome assembly. Numerous small sequence variants were detected and the ploidy of the cultivar presented here was determined as triploid based on sequence variant frequencies. Illumina sequence data also revealed a duplication of a large segment on the long arm of chromosome 2 in the Dwarf Cavendish genome. Comparison against previously sequenced cultivars provided evidence that this duplication is unique to Dwarf Cavendish. Although no functional relevance of this duplication was identified, this example shows the potential of plants to tolerate such aneuploidies.


Assuntos
Duplicação Cromossômica , Musa/genética , Aneuploidia , Cromossomos de Plantas/genética
20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1199-1202, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31813147

RESUMO

OBJECTIVE: To carry out genetic testing for a boy presenting with mental retardation and hypoplasia. METHODS: Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism based array (SNP-array) were used to analyze the boy and his parents. RESULTS: SNP-array has detected a 25.7 Mb microduplication at 2q33.3q36.3 in the boy. Chromosomal karyotyping and FISH analysis indicated that his mother had a karyotype of 46,XX,ish ins(11;2) (p15;q33q36), and that the boy has carried an abnormal chromosome 11 derived from the maternal translocation. The karyotype of the boy was ascertained as 46,XY,ish der(11)ins(11;2) (p15;q33q36)mat. CONCLUSION: SNP-array combined with G-banding and FISH can delineate the cryptic translocation and is valuable for the assessment of recurrence risk for subsequent pregnancies.


Assuntos
Hipospadia/genética , Deficiência Intelectual/genética , Cariotipagem , Criança , Bandeamento Cromossômico , Duplicação Cromossômica , Feminino , Testes Genéticos , Humanos , Hibridização in Situ Fluorescente , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez , Translocação Genética
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