scholarly journals Difficulties of Prenatal Genetic Counseling for a Subsequent Child in a Family With Multiple Genetic Variations

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Xuan Huang ◽  
Gwo-Chin Ma ◽  
Ming Chen ◽  
Wen-Fang Li ◽  
Steven W. Shaw
Keyword(s):  
Genetic Counseling ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Genetic Variations ◽  
Epileptic Encephalopathy ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Prenatal Counseling ◽  
Ethical Implications ◽  
Genome Wide

Many parents with a disabled child caused by a genetic condition appreciate the option of prenatal genetic diagnosis to understand the chance of recurrence in a future pregnancy. Genome-wide tests, such as chromosomal microarray analysis and whole-exome sequencing, have been increasingly used for prenatal diagnosis, but prenatal counseling can be challenging due to the complexity of genomic data. This situation is further complicated by incidental findings of additional genetic variations in subsequent pregnancies. Here, we report the prenatal identification of a baby with a MECP2 missense variant and 15q11.2 microduplication in a family that has had a child with developmental and epileptic encephalopathy caused by a de novo KCNQ2 variant. An extended segregation analysis including extended relatives, in addition to the parents, was carried out to provide further information for genetic counseling. This case illustrates the challenges of prenatal counseling and highlights the need to understand the clinical and ethical implications of genome-wide tests.

scholarly journals Genetic counseling for a prenatal diagnosis of structural chromosomal abnormality with high-resolution analysis using a single nucleotide polymorphism microarray

2016 ◽  
Vol 6 (3) ◽  
Author(s):  
Akiko Takashima ◽  
Naoki Takeshita ◽  
Toshihiko Kinoshita
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Genetic Counseling ◽  
Chromosomal Abnormality ◽  
Chromosomal Rearrangements ◽  
Genetic Diagnosis ◽  
Chromosomal Microarray ◽  
Normal Male ◽  
Chromosomal Microarray Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

A 41-year old pregnant woman underwent amniocentesis to conduct a conventional karyotyping analysis; the analysis reported an abnormal karyotype: 46,XY,add(9)(p24). Chromosomal microarray analysis (CMA) is utilized in prenatal diagnoses. A single nucleotide polymorphism microarray revealed a male fetus with balanced chromosomal translocations on 9p and balanced chromosomal rearrangements, but another chromosomal abnormality was detected. The fetus had microduplication. The child was born as a phenotypically normal male. CMA is a simple and informative procedure for prenatal genetic diagnosis. CMA is the detection of chromosomal variants of unknown clinical significance; therefore, genetic counseling is important during prenatal genetic testing.

scholarly journals Mosaic duplication of 8q24.1q24.3 detected by chromosomal microarray but not karyotyping in two unrelated fetuses with cardiac defects

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaobin Lin ◽  
Shufang Huang ◽  
Xueling Ou ◽  
Heng Gu ◽  
Yonghua Wang ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Copy Number ◽  
Genetic Disorders ◽  
Genetic Diagnosis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Cardiac Defects ◽  
Prenatal Genetic Diagnosis ◽  
Tumor Tissues ◽  
Number Variation

Abstract Background Discordance between traditional cytogenetic and molecular cytogenetic tests is rare but not uncommon. The explanation of discordance between two genetic methods is difficult but especially important for genetic counseling, particularly for prenatal genetic diagnosis. Case presentation Two unrelated fetuses were diagnosed with cardiac defects by prenatal ultrasound examination, and invasive cordocentesis was performed to obtain cord blood samples for prenatal genetic diagnosis. For both fetuses, chromosomal microarray analysis (CMA) detected a novel approximately 27-Mb mosaic duplication with a high copy number of approximately six to seven copies on chromosome 8q24.1q24.3 that was not identified by karyotyping. To exclude artificial errors and validate laboratory detection results, multiple procedures including copy number variation sequencing, fluorescence in situ hybridization, and short tandem repeat and single-nucleotide polymorphism genotype comparison were performed, confirming the discordant results between CMA and karyotyping. The potential causes of discordance between CMA and karyotyping using fetal blood lymphocytes are discussed; we suggest that extrachromosomal DNA or cell-free DNA fragmentation originating from certain tumor tissues with 8q24.1q24.3 duplication might deserve further investigation. Conclusions This study may be helpful for prenatal evaluation and genetic counseling for subsequent patients with similar mosaic 8q24.1q24.3 duplications. Additionally, more cases and further research are needed to understand whether mosaic 8q24.1q24.3 duplication is associated with certain genetic disorders and to investigate the causes of discordance between molecular and morphological methods.

scholarly journals When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations

2017 ◽  
Vol 20 (1) ◽  
pp. 128-131 ◽  
Author(s):  
Idit Maya ◽  
Reuven Sharony ◽  
Shiri Yacobson ◽  
Sarit Kahana ◽  
Josepha Yeshaya ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Microarray Analysis ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis

scholarly journals Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Liu ◽  
Hongqian Liu ◽  
Jianlong Liu ◽  
Ting Bai ◽  
Xiaosha Jing ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Prenatal Diagnosis ◽  
Pregnant Women ◽  
Prenatal Screening ◽  
Chromosomal Abnormalities ◽  
Detection Methods ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Non Invasive

BackgroundOur aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS).MethodsA retrospective analysis was performed on pregnant women who had failed NIPS tests.ResultsAmong the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively.ConclusionPrenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses.

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.

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 Clinical features and genetic analysis of two Chinese families with X-linked ichthyosis

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096229
Author(s):  
Wanqin Xie ◽  
Haiyan Zhou ◽  
Lin Zhou ◽  
Yun Gong ◽  
Jiwu Lin ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Venous Blood ◽  
Mendelian Inheritance ◽  
Hunan Province ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Entire Body ◽  
Chinese Families ◽  
The Family ◽  
Atypical Phenotype

Objective Recessive X-linked ichthyosis (RXLI) caused by deficiency of the steroid sulfatase gene ( STS) has a reported prevalence of 1/2000 to 1/6000. The present study aimed to characterize the phenotypes and genotypes of two Chinese families with RXLI. Methods The patients were referred to the Family Planning Research Institute of Hunan Province for genetic counseling. Their skin phenotypes were photographed, and venous blood was drawn and used for chromosomal microarray analysis (CMA). Results The skin phenotype of the proband from the first family was characterized by generalized skin dryness and scaling, with noticeable dark brown, polygonal scales on his trunk and extensor surfaces of his extremities. The proband from the second family had an atypical phenotype showing mild skin dryness over his entire body, slight scaling on his abdomen, and small skin fissures on his arms and legs. No mental disability or developmental anomaly was noted in either proband. CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving four Online Mendelian Inheritance in Man-listed genes including STS. Conclusions Our findings add knowledge to the genotype and phenotype spectrum of RXLI, which may be helpful in genetic counseling and prenatal diagnosis.

Sign in / Sign up

Export Citation Format

Share Document