Genetic counseling in direct-to-consumer exome sequencing: a case report.
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ABSTRACT:
SUBMITTER: van den Berg S
PROVIDER: S-EPMC4156788 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Genetic counseling in direct-to-consumer exome sequencing: a case report.
van den Berg Saskia S Shen Yaoqing Y Jones Steven J M SJ Gibson William T WT
Journal of genetic counseling 20140624 5
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Project description:ObjectiveGrowing use of clinical exome sequencing (CES) has led to an increased burden of genomic education. Self-guided educational tools can minimize the educational burden for genetic counselors (GCs). The effectiveness of these tools must be evaluated.MethodsParents of patients offered CES were randomized to watch educational videos before their visit or to receive routine care. Parents and GCs were surveyed about their experiences following the sessions. The responses of the video (n = 102) and no-video (n = 105) groups were compared.ResultsGCs reported no significant differences between parents in the video and no-video groups on genetics knowledge or CES knowledge. In contrast, parents' scores on genetics knowledge questions were lower in the video than no-video group (p = 0.007). Most parents reported the videos were informative, and the groups did not differ in satisfaction with GCs or decisions to have CES.ConclusionGCs and parents perceived the videos to be beneficial. However, lower scores on genetics knowledge questions highlight the need for careful development of educational tools.Practice implicationsEducational tools should be developed and assessed for effectiveness with the input of all stakeholders before widespread implementation. Better measures of the effectiveness of these educational tools are needed.
| S-EPMC9667716 | biostudies-literature
Project description:The discovery of rare genetic variation through different gene sequencing methods is a very challenging subject in the field of human genetics. A case of a 1-year-old boy with metabolic acidosis and hypokalemia, a small penis, growth retardation, and G-6PD deficiency was reported. Since the clinical symptoms are complex and seem uncorrelated, the authors hypothesized that the child had chromosome or gene problems, and exome sequencing (ES) was applied to samples from him and his parents. Three main locus mutations in three genes were found in the proband, including SLC4A1, FGFR1, and G6PD genes. A missense mutation (c.1766G>T, p.R589 L) was found in exon 14 of SLC4A1 gene, which was a de novo mutation. Another missense mutation (c.1028 A>G, p.H343R) was found in exon 9 of FGFR1 gene, which was also a de novo mutation. These findings further demonstrate the utility of ES in the diagnosis of rare diseases.
| S-EPMC8567987 | biostudies-literature
Project description:BackgroundZinner syndrome is a rare congenital malformation of the male genitourinary system, characterized by a triad: seminal vesicle cyst, unilateral renal agenesis, and ipsilateral ejaculatory duct obstruction. The etiology of this uncommon disease remains largely elusive; however, genetic mutations may contribute to its development. In this report, we present a case of symptomatic Zinner syndrome that was surgically treated, alongside an investigation into the potential genetic basis of the syndrome via whole exome sequencing.Case presentationWe report the case of an 18-year-old male presenting with urinary pain and was diagnosed with right renal agenesis and a left seminal vesicle cyst following comprehensive imaging. The patient also experienced perineal pain and urgency, without symptoms of frequent urination, dysuria, or hematuria, and no familial history of genitourinary anomalies was documented. He successfully underwent laparoscopic resection of a pelvic mass, with pathological examination confirming a seminal vesicle cyst. Postoperative recovery was uneventful. Whole exome sequencing of blood and tissue samples highlighted myeloma overexpressed gene (MYEOV), B melanoma antigen family member (BAGE), and N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) as potential mutated genes related to Zinner syndrome. Additionally, two predisposing genetic variants were identified.ConclusionsZinner syndrome is a rare condition commonly diagnosed via various imaging modalities. Surgical resection remains the most effective treatment for symptomatic cases. Gene sequencing provides valuable insights into the genetic etiology of Zinner syndrome, enhancing our understanding and potentially guiding future diagnostic approaches.
| S-EPMC11895205 | biostudies-literature
Project description:BackgroundDespite advances in routine prenatal cytogenetic testing, most anomalous fetuses remain without a genetic diagnosis. Exome sequencing (ES) is a molecular technique that identifies sequence variants across protein-coding regions and is now increasingly used in clinical practice. Fetal phenotypes differ from postnatal and, therefore, prenatal ES interpretation requires a large amount of data deriving from prenatal testing. The aim of our study was to present initial results of the implementation of ES to prenatal diagnosis in Polish patients and to discuss its possible clinical impact on genetic counseling.MethodsIn this study we performed a retrospective review of all fetal samples referred to our laboratory for ES from cooperating centers between January 2017 and June 2021.ResultsDuring the study period 122 fetuses were subjected to ES at our institution. There were 52 abnormal ES results: 31 in the group of fetuses with a single organ system anomaly and 21 in the group of fetuses with multisystem anomalies. The difference between groups was not statistically significant. There were 57 different pathogenic or likely pathogenic variants reported in 33 different genes. The most common were missense variants. In 17 cases the molecular diagnosis had an actual clinical impact on subsequent pregnancies or other family members.ConclusionsExome sequencing increases the detection rate in fetuses with structural anomalies and improves genetic counseling for both the affected couple and their relatives.
| S-EPMC9140952 | biostudies-literature
Project description: Not available
| S-EPMC9426147 | biostudies-literature
Project description:The yield of genetic prenatal diagnosis has been notably improved by introducing whole genome chromosomal microarray (CMA) and prenatal exome sequencing (pES). However, together with increased numbers of diagnoses made, the need to manage challenging findings such as variants of unknown significance (VUS) and incidental findings (IF) also increased. We have summarized the current guidelines and recommendations and we have shown current solutions used in our tertiary center in the Netherlands. We discuss four of the most common clinical situations: fetus with normal pES results, fetus with a pathogenic finding explaining the fetal phenotype, fetus with a variant of uncertain clinical significance fitting the phenotype and fetus with a variant leading to an incidental diagnosis. Additionally, we reflect on solutions in order to facilitate genetic counseling in an NGS-era.
| S-EPMC10198275 | biostudies-literature
Project description:Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that these mutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in the COMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH.
| S-EPMC10702128 | biostudies-literature
Project description:Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer‑predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation‑specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio‑based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy‑number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio‑based ES as a complex approach for the molecular diagnostics of rare pediatric diseases.
| S-EPMC10119849 | biostudies-literature
Project description:Human Papillomavirus (HPV) related Multiphenotypic Sinonasal Carcinoma (HMSC) is a rare tumor with features of both atypical squamous cell and adenoid cystic carcinoma, making diagnosis challenging. Approximately 80% of HMSC cases carries HPV type 33 followed by type 35. We present a patient with HMSC. Pathological classification was aided by immunohistochemistry (IHC). The presence of HPV-DNA was tested using PCR and HPV E6/E7 expression by RNA in situ hybridization (RNA ISH). Whole exome sequencing (WES) was used to identify somatic gene mutations and copy number alterations. A 55-year-old male presented with an HMSC in the right nostril. Histological examination showed a solid basaloid subtype with mucinous spaces and ductal structures. IHC showed positive staining for SOX-10, SMA, p40, p63, PanCK, CK8 and MYB. Diffuse positive staining for p16 was observed and PCR and RNA ISH indicated the presence of HPV type 35. The patient was treated with endoscopic surgery and radiotherapy and is currently alive and recurrence-free after 16 months of follow-up. WES revealed 38 somatic sequence variants and several chromosomal regions with copy number alterations, including a copy number gain at 6q23 where MYB is located. EP300, ZNF22, ZNF609 and LRIG3 are some of the genes whose mutations were indicated as probably pathogenic. We did not find mutations predictive for drug response according to the ESMO Scale for Clinical Actionability of Molecular Targets database. This is the first report of WES analysis of an HMSC, in this case associated with HPV type 35. The detected mutation in EP300 and the overexpression of MYB may serve as molecular targets for personalized therapy.
| S-EPMC11419970 | biostudies-literature
Project description:Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling. Case Report: A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (-α3.7/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (-α3.7/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses. Conclusion: This study enlarges the mutation spectrum of β-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.
| S-EPMC8194298 | biostudies-literature