Genomic imbalance in a patient with two balanced translocations and abnormal phenotype

2021 ◽  
pp. 40-43
Author(s):  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
А.Ф. Муртазина ◽  
Н.В. Шилова
Keyword(s):  
Clinical Symptoms ◽  
Cytogenetic Study ◽  
Molecular Genetic ◽  
Break Point ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Chromosome 6 ◽  
Molecular Genetic Study ◽  
Psychomotor Delay ◽  
Balanced Translocations

Представлены клинические и молекулярно-генетические результаты обследования пациента с задержкой психомоторного развития, аномалиями фенотипа и множественными врожденными пороками систем и органов. При стандартном цитогенетическом исследовании определены две реципрокные транслокации между хромосомами 2 и 6 и хромосомами 7 и 11, подтвержденные FISH-методом. Хромосомный микроматричный анализ позволил выявить делецию 6q14.1 в точке разрыва на длинном плече хромосомы 6. Делеция включает несколько десятков генов, в том числе гены PHIP, FILIP1, MYO6, HTR1B, IMPG1, EVOLV4, TENT5A, которые вероятнее всего ассоциированы с клиническими проявлениями у пациента. The results of clinical and molecular genetic study of the patient with psychomotor delay, phenotype abnormalities and multiple congenital malformations of systems and organs are presented. A standard cytogenetic study determined a double translocation between chromosomes 2 and 6 and chromosomes 7 and 11, confirmed by the FISH method. Chromosomal microarray analysis revealed a deletion of 6q14.1 region at the break point on the long arm of chromosome 6. The deletion involves several dozen genes, including PHIP, FILIP1, MYO6, HTR1B, IMPG1, EVOLV4, TENT5A genes, which are most likely associated with clinical symptoms in the patient.

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.

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.

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.

scholarly journals Chromosomal Microarray Analysis as First-Tier Genetic Test for Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Chia-Hsiang Chen ◽  
Min-Chih Cheng ◽  
Tsung-Ming Hu ◽  
Lieh-Yung Ping
Keyword(s):  
Genetic Testing ◽  
Microarray Analysis ◽  
Copy Number ◽  
Genetic Test ◽  
Molecular Genetic ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Clinical Settings ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders

Schizophrenia is a chronic, devastating mental disorder with complex genetic components. Given the advancements in the molecular genetic research of schizophrenia in recent years, there is still a lack of genetic tests that can be used in clinical settings. Chromosomal microarray analysis (CMA) has been used as first-tier genetic testing for congenital abnormalities, developmental delay, and autism spectrum disorders. This study attempted to gain some experience in applying chromosomal microarray analysis as a first-tier genetic test for patients with schizophrenia. We consecutively enrolled patients with schizophrenia spectrum disorder from a clinical setting and conducted genome-wide copy number variation (CNV) analysis using a chromosomal microarray platform. We followed the 2020 “Technical Standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)” to interpret the clinical significance of CNVs detected from patients. We recruited a total of 60 patients (36 females and 24 males) into this study. We detected three pathogenic CNVs and one likely pathogenic CNV in four patients, respectively. The detection rate was 6.7% (4/60, 95% CI: 0.004–0.13), comparable with previous studies in the literature. Also, we detected thirteen CNVs classified as uncertain clinical significance in nine patients. Detecting these CNVs can help establish the molecular genetic diagnosis of schizophrenia patients and provide helpful information for genetic counseling and clinical management. Also, it can increase our understanding of the pathogenesis of schizophrenia. Hence, we suggest CMA is a valuable genetic tool and considered first-tier genetic testing for schizophrenia spectrum disorders in clinical settings.

First Report of Low-Rate Mosaicism for 20q11.21q12 Deletion and Delineation of the Associated Disorder

2018 ◽  
Vol 156 (2) ◽  
pp. 87-94
Author(s):  
Sara Loddo ◽  
Viola Alesi ◽  
Silvia Genovese ◽  
Valeria Orlando ◽  
Chiara Calacci ◽  
...  
Keyword(s):  
Growth Retardation ◽  
Snp Array ◽  
Small Region ◽  
Growth Delay ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Psychomotor Delay ◽  
Feeding Difficulties ◽  
First Case ◽  
Snp Array Analysis

Interstitial deletions of the long arm of chromosome 20 are very rare, with only 12 reported patients harboring the 20q11.2 microdeletion and presenting a disorder characterized by psychomotor and growth delay, dysmorphisms, and brachy-/clinodactyly. We describe the first case of mosaic 20q11.2 deletion in a 5-year-old girl affected by mild psychomotor delay, feeding difficulties, growth retardation, craniofacial dysmorphisms, and finger anomalies. SNP array analysis disclosed 20% of cells with a 20q11.21q12 deletion, encompassing the 20q11.2 minimal critical region and the 3 OMIM disease-causing genes GDF5, EPB41L1, and SAMHD1. We propose a pathogenic role of other genes mapping outside the small region of overlap, in particular GHRH (growth hormone releasing hormone), whose haploinsufficiency could be responsible for the prenatal onset of growth retardation which is shared by half of these patients. Our patient highlights the utility of chromosomal microarray analysis to identify low-level mosaicism.

scholarly journals Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes

2021 ◽  
Author(s):  
Mohamed Al-Hamed ◽  
Wesam Kurdi ◽  
Rubina Khan ◽  
Maha Tulbah ◽  
Maha AlNemer ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Microarray Analysis ◽  
Molecular Genetic ◽  
Genetic Diagnostics ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Fetal Anomalies ◽  
Fetal Abnormalities ◽  
Pathogenic Variants ◽  
Structural Anomalies

Abstract Background Fetal abnormalities are detected in 3% of all pregnancies and are responsible for approximately 20% of all perinatal deaths. Chromosomal microarray analysis (CMA) and exome sequencing (ES) are widely used in prenatal settings for molecular genetic diagnostics with variable diagnostic yields. In this study, we aimed to determine the diagnostic yield of trio-ES in detecting the cause of fetal abnormalities within a highly consanguineous population. Methods In families with a history of congenital anomalies, a total of 119 fetuses with structural anomalies were recruited and DNA from invasive samples were used together with parental DNA samples for trio-ES and CMA. Data were analysed to determine possible underlying genetic disorders associated with observed fetal phenotypes. Results The cohort had a known consanguinity of 81%. Trio-ES led to diagnostic molecular genetic findings in 59 fetuses (with pathogenic / likely pathogenic variants) most with multisystem or renal abnormalities. CMA detected chromosomal abnormalities compatible with the fetal phenotype in another 7 cases. Monogenic ciliopathy disorders with an autosomal recessive inheritance were the predominant cause of multisystem fetal anomalies (24/59 cases, 40.7%) with loss of function variants representing the vast majority of molecular genetic abnormalities. Heterozygous de novo pathogenic variants were found in 4 fetuses. A total of 23 novel variants predicted to be associated with the phenotype were detected. Conclusion Prenatal trio-ES and CMA detected likely causative molecular genetic defects in a total of 55% of families with fetal anomalies confirming the diagnostic utility of trio-ES and CMA as first line genetic test in the prenatal diagnosis of multisystem fetal anomalies including ciliopathy syndromes.

Challenges in the differential diagnosis of multiple endocrine neoplasia syndrome type 1 with isolated family hyperparathyroidism

2020 ◽  
Vol 98 (3) ◽  
pp. 218-225
Author(s):  
J. A. Krupinova ◽  
N. G. Mokrysheva ◽  
N. Y. Kalinchenko ◽  
A. K. Eremkina ◽  
A. N. Polyakov ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Molecular Genetic ◽  
Pancreatic Neuroendocrine Tumor ◽  
Family Type ◽  
Dynamic Monitoring ◽  
Heterozygous Mutation ◽  
Molecular Genetic Study ◽  
Men 1 ◽  
Endocrine Neoplasia

Multiple endocrine neoplasia type 1 (MEN-1) is the most common cause of the hereditary type of primary hyperparathyroidism (PHPT). If a family type of PHPT is suspected, a dynamic monitoring of patients and their close relatives should be carried out throughout their lives. We present a clinical case of a family in which four members of a pedigree were diagnosed with familial isolated hyperparathyroidism (FIHP). The diagnosis was changed to MEN-1, because it appeared that one of the patients had pancreatic neuroendocrine tumor. Molecular genetic study of MEN1 by direct by means of Sanger sequencing revealed that six family members had a new heterozygous mutation in exon 9: s. 1252 G> T p. D418Y.

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