Molecular Cytogenetics最新文献

{"title":"Correction: X chromosome rearrangement associated with premature ovarian insufficiency as diagnosed by molecular cytogenetic methods: a case report and review of the literature.","authors":"Zhifang Peng, Renqi Yang, Qing Liu, Binbin Chen, Panpan Long","doi":"10.1186/s13039-024-00694-0","DOIUrl":"10.1186/s13039-024-00694-0","url":null,"abstract":"","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"23"},"PeriodicalIF":1.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal diagnosis in fetal right aortic arch using chromosomal microarray analysis and whole exome sequencing: a Chinese single-center retrospective study.","authors":"Lu Zhang, Ruibin Huang, Hang Zhou, Xiaomei Lin, Fei Guo, Xiangyi Jing, Yongling Zhang, Fucheng Li, Fatao Li, Qiuxia Yu, Dan Wang, Guilan Chen, Fang Fu, Min Pan, Jin Han, Dongzhi Li, Ru Li","doi":"10.1186/s13039-024-00691-3","DOIUrl":"https://doi.org/10.1186/s13039-024-00691-3","url":null,"abstract":"<p><strong>Background: </strong>Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA.</p><p><strong>Results: </strong>Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith-Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01).</p><p><strong>Conclusions: </strong>We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"22"},"PeriodicalIF":1.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome - evaluation of a large cohort in India.","authors":"Vivi M Srivastava, Sukesh Chandran Nair, Melvin Joy, Marie-Therese Manipadam, Uday P Kulkarni, Anup J Devasia, N A Fouzia, Anu Korula, Kavitha M Lakshmi, L Jeyaseelan, Aby Abraham, Alok Srivastava","doi":"10.1186/s13039-024-00687-z","DOIUrl":"https://doi.org/10.1186/s13039-024-00687-z","url":null,"abstract":"<p><strong>Background: </strong>The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available.</p><p><strong>Methods: </strong>We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC).</p><p><strong>Results: </strong>There were 936 patients aged 18-86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1-3% each.</p><p><strong>Conclusion: </strong>The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"21"},"PeriodicalIF":1.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal diagnosis of fetuses with 15q11.2 BP1-BP2 microdeletion in the Chinese population: a seven-year single-center retrospective study.","authors":"Jianlong Zhuang, Na Zhang, Wanyu Fu, Yuying Jiang, Yu'e Chen, Chunnuan Chen","doi":"10.1186/s13039-024-00690-4","DOIUrl":"10.1186/s13039-024-00690-4","url":null,"abstract":"<p><strong>Background: </strong>The 15q11.2 BP1-BP2 microdeletion syndrome is associated with developmental delays, language impairments, neurobehavioral disorders, and psychiatric complications. The aim of the present study was to provide prenatal and postnatal clinical data for 16 additional fetuses diagnosed with the 15q11.2 BP1-BP2 microdeletion syndrome in the Chinese population.</p><p><strong>Methods: </strong>A total of 5,789 pregnancy women that underwent amniocentesis were enrolled in the present study. Both karyotype analysis and chromosomal microarray analysis (CMA) were conducted on these subjects to detect chromosomal abnormalities and copy number variants (CNVs). Whole exome sequencing (WES) was performed to investigate sequence variants in subjects with clinical abnormalities after birth.</p><p><strong>Results: </strong>Sixteen fetuses with 15q11.2 BP1-BP2 microdeletion were identified in the present study, with a detection rate of 0.28% (16/5,789). The 15q11.2 BP1-BP2 microdeletion fragments ranged from 311.8 kb to 849.7 kb, encompassing the NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes. The follow-up results regarding pregnancy outcomes showed that five cases opted for pregnancy termination, while the remaining cases continued with their pregnancies. Subsequent postnatal follow-up indicated that only one case with the 15q11.2 BP1-BP2 microdeletion displayed neurodevelopmental disorders, demonstrating an incomplete penetrance rate of 9.09% (1/11).</p><p><strong>Conclusion: </strong>The majority of fetuses with the 15q11.2 microdeletion exhibit typical features during early childhood, indicating a low penetrance and mild impact. Nonetheless, pregnancies involving fetuses with the 15q11.2 microdeletion require thorough prenatal counseling. Additionally, enhanced supervision and extended postnatal monitoring are warranted for those who choose to proceed with their pregnancies.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"20"},"PeriodicalIF":1.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex genomic rearrangements of the Y chromosome in a premature infant.","authors":"Stephanie A Balow, Alyxis G Coyan, Nicki Smith, Bianca E Russell, Danielle Monteil, Robert J Hopkin, Teresa A Smolarek","doi":"10.1186/s13039-024-00689-x","DOIUrl":"10.1186/s13039-024-00689-x","url":null,"abstract":"<p><strong>Background: </strong>Chromoanagenesis is an umbrella term used to describe catastrophic \"all at once\" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions.</p><p><strong>Case presentation: </strong>We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis.</p><p><strong>Conclusion: </strong>This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"19"},"PeriodicalIF":1.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical features associated with maternal uniparental disomy for chromosome 6.","authors":"Jing-Wen Li, Yan-Jie Qian, Shao-Jia Mao, Yun-Qi Chao, Yi-Fang Qin, Chen-Xi Hu, Zheng-Lan Li, Chao-Chun Zou","doi":"10.1186/s13039-024-00688-y","DOIUrl":"10.1186/s13039-024-00688-y","url":null,"abstract":"<p><strong>Background: </strong>Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further.</p><p><strong>Case presentation: </strong>In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR.</p><p><strong>Conclusions: </strong>The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"18"},"PeriodicalIF":1.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal instability in a patient with ring chromosome 14 syndrome: a case report.","authors":"Juan Pablo Meza-Espinoza, Juan Ramón González-García, Nayeli Nieto-Marín, Liliana Itzel Patrón-Baro, Rosa María González-Arreola, Eliakym Arámbula-Meraz, Julio Benítez-Pascual, Alberto Kousuke De la Herrán-Arita, Claudia Desireé Norzagaray-Valenzuela, Marco Antonio Valdez-Flores, Tomás Adrián Carrillo-Cázares, Verónica Judith Picos-Cárdenas","doi":"10.1186/s13039-024-00686-0","DOIUrl":"10.1186/s13039-024-00686-0","url":null,"abstract":"<p><strong>Background: </strong>Ring chromosome 14 syndrome is a rare disorder primarily marked by early-onset epilepsy, microcephaly, distinctive craniofacial features, hypotonia, intellectual disability, and delay in both development and language acquisition.</p><p><strong>Case presentation: </strong>A 21-year-old woman with a history of epileptic seizures since the age of 1.5 years presented with distinctive craniofacial features, including a prominent and narrow forehead, sparse and short eyebrows, palpebral ptosis, horizontal palpebral fissures, a broad nasal bridge, a prominent nasal tip, a flat philtrum, hypertelorism, midfacial hypoplasia, horizontal labial fissures, a thin upper lip, crowded teeth, an ogival palate, retrognathia, and a wide neck. Additional physical abnormalities included kyphosis, lumbar scoliosis, pectus carinatum, cubitus valgus, thenar and hypothenar hypoplasia, bilateral hallux valgus, shortening of the Achilles tendon on the left foot, and hypoplasia of the labia minora. Chromosomal analysis identified a ring 14 chromosome with breakpoints in p11 and q32.33. An aCGH study revealed a ~ 1.7 Mb deletion on chromosome 14qter, encompassing 23 genes. Genomic instability was evidenced by the presence of micronuclei and aneuploidies involving the ring and other chromosomes.</p><p><strong>Conclusion: </strong>The clinical features of our patient closely resembled those observed in other individuals with ring chromosome 14 syndrome. The most important point was that we were able to verify an instability of the r(14) chromosome, mainly involving anaphasic lags and its exclusion from the nucleus in the form of a micronucleus.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"17"},"PeriodicalIF":1.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenomic description of a Mexican cohort with differences in sex development.","authors":"Grecia C Olivera-Bernal, Marlon De Ita-Ley, Edgar F Ricárdez-Marcial, Luz María Garduño-Zarazúa, Ángel Ricardo González-Cuevas, Omar A Sepúlveda-Robles, Juan Carlos Huicochea-Montiel, Alan Cárdenas-Conejo, Laura Santana-Díaz, Haydeé Rosas-Vargas","doi":"10.1186/s13039-024-00685-1","DOIUrl":"10.1186/s13039-024-00685-1","url":null,"abstract":"<p><strong>Background: </strong>Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500-5500, which can increase to 1:200-300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital.</p><p><strong>Methods: </strong>Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City.</p><p><strong>Results: </strong>One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification.</p><p><strong>Conclusion: </strong>The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"16"},"PeriodicalIF":1.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesomelia-synostoses syndrome: contiguous deletion syndrome, SULF1 haploinsufficiency or enhancer adoption?","authors":"Ingrid Bendas Feres Lima, Lúcia de Fátima Marques de Moraes, Carlos Roberto da Fonseca, Juan Clinton Llerena Junior, Mana Mehrjouy, Niels Tommerup, Elenice Ferreira Bastos","doi":"10.1186/s13039-024-00684-2","DOIUrl":"10.1186/s13039-024-00684-2","url":null,"abstract":"<p><strong>Background: </strong>Mesomelia-Synostoses Syndrome (MSS)(OMIM 600,383) is a rare autosomal dominant disorder characterized by mesomelic limb shortening, acral synostoses and multiple congenital malformations which is described as a contiguous deletion syndrome involving the two genes SULF1 and SLCO5A1. The study of apparently balanced chromosomal rearrangements (BCRs) is a cytogenetic strategy used to identify candidate genes associated with Mendelian diseases or abnormal phenotypes. With the improved development of genomic technologies, new methods refine this search, allowing better delineation of breakpoints as well as more accurate genotype-phenotype correlation.</p><p><strong>Case presentation: </strong>We present a boy with a global development deficit, delayed speech development and an ASD (Asperger) family history, with an apparently balanced \"de novo\" reciprocal translocation [t(1;8)(p32.2;q13)dn]. The cytogenetic molecular study identified a likely pathogenic deletion of 21 kb in the 15q12 region, while mate pair sequencing identified gene-truncations at both the 1p32.2 and 8q13 translocation breakpoints.</p><p><strong>Conclusions: </strong>The identification of a pathogenic alteration on 15q12 involving GABRA5 was likely the main cause of the ASD-phenotype. Importantly, the chr8 translocation breakpoint truncating SLCO5A1 exclude SLCO5A1 as a candidate for MSS, leaving SULF1 as the primary candidate. However, the deletions observed in MSS remove a topological associated domain (TAD) boundary separating SULF1 and SLCO5A1. Hence, Mesomelia-Synostoses syndrome is either caused by haploinsufficiency of SULF1 or ectopic enhancer effects where skeletal/chrondrogenic SULF1 enhancers drive excopic expression of developmental genes in adjacent TADs including PRDM14, NCOA2 and/or EYA1.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"15"},"PeriodicalIF":1.3,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11241779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals TCR rearrangements as predictive factors for exceptional prognosis.","authors":"Libuse Lizcova, Eva Prihodova, Lenka Pavlistova, Karla Svobodova, Ester Mejstrikova, Ondrej Hrusak, Pavla Luknarova, Iveta Janotova, Lucie Sramkova, Jan Stary, Zuzana Zemanova","doi":"10.1186/s13039-024-00682-4","DOIUrl":"10.1186/s13039-024-00682-4","url":null,"abstract":"<p><strong>Background: </strong>T-cell acute lymphoblastic leukemia (T-ALL) represents a rare and clinically and genetically heterogeneous disease that constitutes 10-15% of newly diagnosed pediatric ALL cases. Despite improved outcomes of these children, the survival rate after relapse is extremely poor. Moreover, the survivors must also endure the acute and long-term effects of intensive therapy. Although recent studies have identified a number of recurrent genomic aberrations in pediatric T-ALL, none of the changes is known to have prognostic significance. The aim of our study was to analyze the cytogenomic changes and their various combinations in bone marrow cells of children with T-ALL and to correlate our findings with the clinical features of the subjects and their treatment responses.</p><p><strong>Results: </strong>We performed a retrospective and prospective comprehensive cytogenomic analysis of consecutive cohort of 66 children (46 boys and 20 girls) with T-ALL treated according to BFM-based protocols and centrally investigated cytogenetics and immunophenotypes. Using combinations of cytogenomic methods (conventional cytogenetics, FISH, mFISH/mBAND, arrayCGH/SNP and MLPA), we identified chromosomal aberrations in vast majority of patients (91%). The most frequent findings involved the deletion of CDKN2A/CDKN2B genes (71%), T-cell receptor (TCR) loci translocations (27%), and TLX3 gene rearrangements (23%). All chromosomal changes occurred in various combinations and were rarely found as a single abnormality. Children with aberrations of TCR loci had a significantly better event free (p = 0.0034) and overall survival (p = 0.0074), all these patients are living in the first complete remission. None of the abnormalities was an independent predictor of an increased risk of relapse.</p><p><strong>Conclusions: </strong>We identified a subgroup of patients with TCR aberrations (both TRA/TRD and TRB), who had an excellent prognosis in our cohort with 5-year EFS and OS of 100%, regardless of the presence of other abnormality or the translocation partner. Our data suggest that escalation of treatment intensity, which may be considered in subsets of T-ALL is not needed for nonHR (non-high risk) patients with TCR aberrations.</p>","PeriodicalId":19099,"journal":{"name":"Molecular Cytogenetics","volume":"17 1","pages":"14"},"PeriodicalIF":1.3,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11118568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}