A maternally inherited Interstitial Xq21 deletion associated with deafness and mental retardation syndrome in a male patient

2021 ◽  
pp. 50-52
Author(s):  
Ж.Г. Маркова ◽  
М.Е. Миньженкова ◽  
Н.А. Демина ◽  
Н.В. Шилова
Keyword(s):  
Mental Retardation ◽  
Speech Development ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Chromosomal Microarray Analysis ◽  
Mild Phenotype ◽  
Number Of Patients ◽  
Causative Effect ◽  
Female Carriers ◽  
Apparently Healthy

Клиническое значение делеции района q21 хромосомы X у мужчин все еще плохо изучено. Было показано, что делеция Xq21, включающая гены POU3F4, CHM и ZNF711, может приводить к глухоте, умственной отсталости и хороидеремии. Несмотря на тяжелые симптомы, наблюдаемые у пробандов-мужчин, большинство носителей женского пола бессимптомны или имеют незначительные фенотипические проявления. Представлена клиническая и молекулярно-цитогенетическая характеристика случая делеции района q21.1-q21.31 хромосомы X, выявленной при проведении хромосомного микроматричного анализа у пациента с задержкой психоречевого развития, лицевыми дизморфиями и тугоухостью. Такая же делеция была выявлена у практически здоровой матери. Наши данные способствуют дальнейшему пониманию корреляции между делецией Xq21 и аномальным фенотипом. Deletions on the X chromosome can lead to serious birth defects. Deletions in Xq21 cause various congenital defects in males including choroideremia, deafness and mental retardation, depending on their size and gene content. Only a limited number of patients with Xq21 deletions has been reported. It has been shown that deletions of the adjacent Xq21 genes, including the POU3F4, CHM and ZNF711 genes, can lead to deafness and mental retardation syndrome and choroideremia. Despite the severe symptoms exhibited by male probands, most female carriers are asymptomatic or exhibit only a mild phenotype. The article presents the clinical and molecular-cytogenetic characteristics of a case of deletion of the Xq21.1-q21.31 region of chromosome X, revealed during chromosomal microarray analysis in a patient with delayed psycho-speech development, facial dysmorphisms and hearing loss. The same deletion was found in an apparently healthy mother. Our study confirms the causative effect between the Xq21 deletion in males and choroideremia, deafness and mental retardation.

scholarly journals Prenatal diagnosis of a 4.5-Mb deletion at chromosome 4q35.1q35.2: Case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gefei Xiao ◽  
Xianrong Qiu ◽  
Yuqiu Zhou ◽  
Gongjun Tan ◽  
Yao Shen
Keyword(s):  
Single Copy ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Banding Technique ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Protein Coding ◽  
Genotype Phenotype Correlation ◽  
Number Variation

Abstract Objective We present a genetic analysis of an asymptomatic family with a 4q terminal deletion; we also review other similar published studies and discuss the genotype–phenotype correlation. Methods A karyotype analysis was performed on the amniotic fluid cells of a woman at 24 weeks of pregnancy and peripheral blood lymphocytes from both parents and their older son with the conventional G-banding technique. Chromosomal microarray analysis (CMA) testing was carried out for both parents and the fetus to analyze copy number variation (CNV) in the whole genome. Results The results showed no abnormalities in the karyotypes of the father and older son, and the karyotypes of the mother and fetus were 46,XX,del(4)(q35.1) and 46,XY,del(4)(q35.1), respectively. CMA results showed a partial deletion at the 4q terminus in both the fetus and mother. The deletion region of the fetus was arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) × 1; the loss size of the CNV was approximately 4.5 Mb and involved 14 protein-coding genes, namely, CYP4V2, F11, FAM149A, FAT1, FRG1, FRG2, KLKB1, MTNR1A, PDLIM3, SORBS2, TLR3, TRIML1, TRIML2, and ZFP42. No variation on chromosome 4 was detected in the father’s CMA results. Conclusion Deletion of the 4q subtelomeric region is a familial variation. The arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) region single-copy deletion did not cause obvious congenital defects or mental retardation. The application of high-resolution genetic testing technology combined with the analysis of public genetic database information can more clearly elucidate the genotype–phenotype correlation of the disease and provide support for both prenatal and postnatal genetic counseling.

A case of deletion 8q22.2q22.3 in a child with de novo balanced translocation t(1;6)

2021 ◽  
pp. 49-56
Author(s):  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
И.В. Анисимова ◽  
И.В. Канивец ◽  
Н.В. Шилова
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Current Trend ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Chromosomal Microarray Analysis ◽  
Balanced Translocation ◽  
Genomic Imbalance ◽  
Abnormal Phenotype ◽  
Balanced Translocations

Выяснение этиопатогенеза аномального фенотипа у пациентов со сбалансированными транслокациями является актуальным аспектом в современной клинической цитогенетике. Формирование аномалий развития может быть ассоциировано с наличием скрытого геномного дисбаланса как в точках разрывов, так и на хромосомах, не задействованных в перестройке. Целью данного исследования явилась этиологическая диагностика геномного дисбаланса у пациента со сбалансированной транслокацией и аномалиями развития. Для детекции геномного дисбаланса у пациента со сбалансированной транслокацией использовали хромосомный микроматричный анализ (ХМА) и FISH-исследование. У пациента со сбалансированной транслокацией при ХМА была выявлена делеция на хромосоме 8, не задействованной в транслокации. Таким образом, в статье представлен новый случай делеции 8q22.2q22.3 у пациента со сбалансированной транслокацией t(1;6) и аномалиями развития вследствие делеции. Identification of the etiopathogenesis of the abnormal phenotype in patients with balanced translocations is current trend in cytogenetic laboratories. The formation of developmental anomalies can be associated with the presence of a cryptic genomic imbalance both at breakpoints and on chromosomes not involved in rearrangements.The aim of this study is diagnostics of genomic imbalance in a patient with balanced translocation and abnormal phenotype. The case was characterized by GTG-banding, chromosomal microarray analysis and FISH diagnosis. We present a new case of deletion 8q22.2-q22.3 in child with balanced translocation t(1;6) and developmental delay/congenital defects due to deletion.

Clinical and molecular-genetics diagnosis of microdeletion Xp11.4

2020 ◽  
pp. 35-36
Author(s):  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
Т.В. Маркова ◽  
Н.В. Шилова
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Speech Development ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Cerebellar Hypoplasia ◽  
Pontocerebellar Hypoplasia ◽  
Molecular Genetic Study ◽  
Psychomotor Delay ◽  
Study Results

Представлены клинические и молекулярно-генетические результаты обследования девочки с задержкой психомоторного, речевого и физического развития, микроцефалией, гипоплазией моста и мозжечка. Хромосомный микроматричный анализ позволил выявить делецию Хр11.4, затрагивающую ген CASK, который ассоциирован с клиническими проявлениями MICPCH-синдрома (mental retardation and microcephaly with pontine and cerebellar hypoplasia). Сlinical and molecular-genetic study results of a girl with developemental and psychomotor delay, lack of speech development, microcephaly, and pontocerebellar hypoplasia are presented. Chromosomal microarray analysis revealed a deletion of Xp11.4 affecting the CASK gene that is associated with clinical manifestations of MICPCH-syndrome.

Chromosomal Microarray Analysis in a Girl With Mental Retardation and Spina Bifida

2011 ◽  
Vol 44 (1) ◽  
pp. 65-68 ◽  
Author(s):  
Inesse Ben Abdallah ◽  
Hanene Hannachi ◽  
Najla Soyah ◽  
Ali Saad ◽  
Hatem Elghezal
Keyword(s):  
Mental Retardation ◽  
Spina Bifida ◽  
Microarray Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis

scholarly journals Two Patients with Complex Rearrangements Suggestive of Germline Chromoanagenesis

2020 ◽  
Vol 160 (11-12) ◽  
pp. 671-679
Author(s):  
Priyanka Arya ◽  
Jennelle C. Hodge ◽  
Peggy A. Matlock ◽  
Gail H. Vance ◽  
Amy M. Breman
Keyword(s):  
Microarray Analysis ◽  
Copy Number ◽  
Muscle Tone ◽  
Chromosome Region ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Single Chromosome ◽  
Complex Rearrangement ◽  
Number Of Patients ◽  
Normal Copy Number

Chromoanagenesis, a phenomenon characterized by complex chromosomal rearrangement and reorganization events localized to a limited number of genomic regions, includes the subcategories chromothripsis, chromoanasynthesis, and chromoplexy. Although definitions of these terms are evolving, constitutional chromoanagenesis events have been reported in a limited number of patients with variable phenotypes. We report on 2 cases with complex genomic events characterized by multiple copy number gains and losses confined to a single chromosome region, which are suggestive of constitutional chromoanagenesis. Case 1 is a 43-year-old male with intellectual disability and recently developed generalized tonic-clonic seizures. Chromosomal microarray analysis identified a complex rearrangement involving chromosome region 14q31.1q32.2, consisting of 16 breakpoints ranging in size from 0.2 to 6.2 Mb, with 5 segments of normal copy number present between these alterations. Interestingly, this case represents the oldest known patient with a complex rearrangement indicative of constitutional chromoanagenesis. Case 2 is a 2-year-old female with developmental delay, speech delay, low muscle tone, and seizures. Chromosomal microarray analysis identified a complex rearrangement consisting of 28 breakpoints localized to 18q21.32q23. The size of the copy number alterations ranged from 0.042 to 5.1 Mb, flanked by 12 small segments of normal copy number. These cases add to a growing body of literature demonstrating complex chromosomal rearrangements as a disease mechanism for congenital anomalies.

scholarly journals Integrated CNV-seq, karyotyping and SNP-array analyses for effective prenatal diagnosis of chromosomal mosaicism

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Na Ma ◽  
Hui Xi ◽  
Jing Chen ◽  
Ying Peng ◽  
Zhengjun Jia ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sex Chromosome ◽  
Snp Array ◽  
Genomic Rearrangements ◽  
Chromosomal Mosaicism ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Low Level ◽  
Autosomal Aneuploidy ◽  
Number Variation

Abstract Background Emerging studies suggest that low‐coverage massively parallel copy number variation sequencing (CNV-seq) more sensitive than chromosomal microarray analysis (CMA) for detecting low-level mosaicism. However, a retrospective back-to-back comparison evaluating accuracy, efficacy, and incremental yield of CNV-seq compared with CMA is warranted. Methods A total of 72 mosaicism cases identified by karyotyping or CMA were recruited to the study. There were 67 mosaic samples co-analysed by CMA and CNV-seq, comprising 40 with sex chromosome aneuploidy, 22 with autosomal aneuploidy and 5 with large cryptic genomic rearrangements. Results Of the 67 positive mosaic cases, the levels of mosaicism defined by CNV-seq ranged from 6 to 92% compared to the ratio from 3 to 90% by karyotyping and 20% to 72% by CMA. CNV-seq not only identified all 43 chromosomal aneuploidies or large cryptic genomic rearrangements detected by CMA, but also provided a 34.88% (15/43) increased yield compared with CMA. The improved yield of mosaicism detection by CNV-seq was largely due to the ability to detect low level mosaicism below 20%. Conclusion In the context of prenatal diagnosis, CNV-seq identified additional and clinically significant mosaicism with enhanced resolution and increased sensitivity. This study provides strong evidence for applying CNV-seq as an alternative to CMA for detection of aneuploidy and mosaic variants.

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