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.

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

2018 ◽  
Vol 154 (4) ◽  
pp. 201-208 ◽  
Author(s):  
Shu Liu ◽  
Zhiqing Wang ◽  
Sisi Wei ◽  
Jinqun Liang ◽  
Nuan Chen ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Gray Matter ◽  
De Novo ◽  
Ring Chromosome ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 6 ◽  
Material Loss ◽  
Ring Chromosome 6

Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

scholarly journals Chromosomal Microarray Analysis in Children with Unexplained Developmental Delay/Intellectual Disability

2018 ◽  
Vol 08 (01) ◽  
pp. 001-009
Author(s):  
Pinar Arican ◽  
Berk Ozyilmaz ◽  
Dilek Cavusoglu ◽  
Pinar Gencpinar ◽  
Kadri Erdogan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Copy Number Variants ◽  
Autism Spectrum ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Genetic Syndromes ◽  
Pathogenic Cnvs ◽  
Spectrum Disorders

AbstractChromosomal microarray (CMA) analysis for discovery of copy number variants (CNVs) is now recommended as a first-line diagnostic tool in patients with unexplained developmental delay/intellectual disability (DD/ID) and autism spectrum disorders. In this study, we present the results of CMA analysis in patients with DD/ID. Of 210 patients, pathogenic CNVs were detected in 26 (12%) and variants of uncertain clinical significance in 36 (17%) children. The diagnosis of well-recognized genetic syndromes was achieved in 12 patients. CMA analysis revealed pathogenic de novo CNVs, such as 11p13 duplication with new clinical features. Our results support the utility of CMA as a routine diagnostic test for unexplained DD/ID.

A 46,XY Female with a 9p24.3p24.1 Deletion and a 8q24.11q24.3 Duplication: A Case Report and Review of the Literature

2019 ◽  
Vol 158 (2) ◽  
pp. 74-82 ◽  
Author(s):  
Valentina Bruni ◽  
Katia Roppa ◽  
Francesca Scionti ◽  
Rosalbina Apa ◽  
Simona Sestito ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Chromosomal Aberration ◽  
Clinical History ◽  
Ambiguous Genitalia ◽  
Chromosome 8 ◽  
Chromosome 9 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Balanced Translocation ◽  
Dysmorphic Features

Deletion of distal 9p is associated with a rare clinical condition characterized by dysmorphic features, developmental delay, and ambiguous genitalia. The phenotype shows variable expressivity and is related to the size of the deletion. 8q24 duplication has been reported in only few cases to date, all showing dysmorphic features and mild psychomotor developmental delay. A case of chromosomal aberration involving a 9p terminal deletion with an 8q duplication has never been reported. Here, we describe a child with a female phenotype, male karyotype, dysmorphic features, ambiguous genitalia, and developmental delay. In order to assess the cause of the patient's phenotype, conventional karyotyping, FISH, and a chromosomal microarray analysis were performed on the patient and her parents. The cytogenetic and molecular analysis revealed an unbalanced chromosomal aberration with a duplication in the long arm of chromosome 8 at 8q24.11q24.3 associated with a distal deletion in the short arm of chromosome 9 at 9p24.3p24.1, derived from a maternal balanced translocation. We compared the clinical picture of our patient with other similar cases reported in the literature and found that some clinical findings, such as strabismus, symphalangism of the first finger, and cubitus valgus, have never been previously associated with 9p deletion or 8q duplication expanding the phenotypic range of this condition. This study is aimed to better define the clinical history and prognosis of patients with this rare chromosomal aberration.

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.

scholarly journals De novo mosaic and partial monosomy of chromosome 21 in a case with superior vena cava duplication

2020 ◽  
Author(s):  
Abul Kalam Azad ◽  
Lindsay Yanakakis ◽  
Samantha Issleb ◽  
Jessica Turina ◽  
Kelli Drabik ◽  
...  
Keyword(s):  
Superior Vena Cava ◽  
De Novo ◽  
Superior Vena ◽  
Vena Cava ◽  
Chromosome 21 ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosomal Anomalies ◽  
Partial Monosomy ◽  
Increased Risk

Abstract Background Full or partial monosomy of chromosome (chr) 21 is a very rare abnormal cytogenetic finding. It is characterized by variable sizes and deletion breakpoints on the long arm (q) of chr 21 that lead to a broad spectrum of phenotypes that include an increased risk of birth defects, developmental delay and intellectual deficit. Case presentation: We report a 37-year-old G1P0 woman initially screened by non-invasive prenatal testing with no positive findings that was followed by an 18-week anatomy scan with a fetal finding of duplication of the superior vena cava (SVC). The medical and family history was otherwise uneventful. After appropriate genetic counseling, amniocentesis was performed to evaluate suspected chromosomal anomalies. Conclusions Fluorescent in situ hybridization revealed loss of one chr 21 signal that was further delineated by chromosomal microarray analysis on uncultured amniocytes as a terminal 10 Mb deletion on chr 21q. Karyotype and microarrays on cultured amniocytes showed two cell lines for a mosaic 21q terminal deletion and monosomy 21. The combined molecular cytogenetics results reported as mos 45,XX,-21[10]/46,XX,del(21)(q22)dn[20].nuc ish(D21S342/D21S341/D21S259 × 1)[100].arr[GRCh37] 21q11.2q22.12(15412676_36272993)x1 ~ 2,21q22.12q22.3(36431283_47612400)x1. Parental chromosomal analysis revealed normal karyotypes. Thus, this was a de novo mosaic full and partial monosomy of chr 21 in a case with SVC duplication. Despite the association of congenital heart disease with monsomy 21 we could not find any published literature or online databases for this cytogenetic abnormality. The patient terminated the pregnancy following the abnormal molecular cytogenetic results due to the possible challenges the baby would face if carried to term.

scholarly journals EIF2AK2-related Neurodevelopmental Disorder With Leukoencephalopathy, Developmental Delay, and Episodic Neurologic Regression Mimics Pelizaeus-Merzbacher Disease

2020 ◽  
Vol 7 (1) ◽  
pp. e539
Author(s):  
Daniel G. Calame ◽  
Meagan Hainlen ◽  
Danielle Takacs ◽  
Leah Ferrante ◽  
Kayla Pence ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Copy Number Variants ◽  
Retrospective Chart Review ◽  
Missense Variant ◽  
Chromosomal Microarray ◽  
Single Nucleotide Variants ◽  
Pelizaeus Merzbacher Disease ◽  
Delayed Myelination

ObjectiveTo demonstrate that de novo missense single nucleotide variants (SNVs) in EIF2AK2 cause a neurodevelopmental disorder with leukoencephalopathy resembling Pelizaeus-Merzbacher disease (PMD).MethodsA retrospective chart review was performed of 2 unrelated males evaluated at a single institution with de novo EIF2AK2 SNVs identified by clinical exome sequencing (ES). Clinical and radiographic data were reviewed and summarized.ResultsBoth individuals presented in the first year of life with concern for seizures and developmental delay. Common clinical findings included horizontal and/or pendular nystagmus during infancy, axial hypotonia, appendicular hypertonia, spasticity, and episodic neurologic regression with febrile viral illnesses. MRI of the brain demonstrated severely delayed myelination in infancy. A hypomyelinating pattern was confirmed on serial imaging at age 4 years for proband 1. In proband 2, repeat imaging at age 13 months confirmed persistent delayed myelination. These clinical and radiographic features led to a strong suspicion of PMD. However, neither PLP1 copy number variants nor pathogenic SNVs were detected by chromosomal microarray and trio ES, respectively. Reanalysis of trio ES identified heterozygous de novo EIF2AK2 missense variant c.290C>T (p.Ser97Phe) in proband 1 and c.326C>T (p.Ala109Val) in proband 2.ConclusionsThe autosomal dominant EIF2AK2-related leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome should be considered in the differential diagnosis for PMD and other hypomyelinating leukodystrophies (HLDs). A characteristic history of developmental regression with febrile illnesses may help distinguish it from other HLDs.

A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect

2018 ◽  
Vol 154 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Beata Aleksiūnienė ◽  
Egle Preiksaitiene ◽  
Aušra Morkūnienė ◽  
Laima Ambrozaitytė ◽  
Algirdas Utkus
Keyword(s):  
Intellectual Disability ◽  
Congenital Heart Defect ◽  
Congenital Heart ◽  
De Novo ◽  
Molecular Karyotyping ◽  
Pcr Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Protein Coding ◽  
Heart Defect

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

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