17p13.3

Genome-wide association studies have identified 270 loci conferring risk for prostate cancer (PCa), yet the underlying biology and clinical impact remain to be investigated. Here we observe an enrichment of transcription factor genes including HNF1B within PCa risk-associated regions. While focused on the 17q12/HNF1B locus, we find a strong eQTL for HNF1B and multiple potential causal variants involved in the regulation of HNF1B expression in PCa. An unbiased genome-wide co-expression analysis reveals PCa-specific somatic TMPRSS2-ERG fusion as a transcriptional mediator of this locus and the HNF1B eQTL signal is ERG fusion status dependent...

Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller-Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of PAFAH1B1 is responsible for the characteristic lissencephaly in MDS. The precise role of YWHAE haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13...

Background: Patients with severe coronavirus disease 2019 (COVID-19) are at an increased risk of acute respiratory distress syndrome and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. Objective: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and noncritically ill COVID-19 patients. Methods: This cross-sectional study recruited 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 from six collection sites across the United Arab Emirates...

This study aimed to re-evaluate the prognostic impact of TP53 mutations and to identify specific chromosomal aberrations as possible prognostic markers in WNT-activated medulloblastoma (WNT-MB). In a cohort of 191 patients with WNT-MBs, mutations in CTNNB1, APC, and TP53 were analyzed by DNA sequencing. Chromosomal copy-number aberrations were assessed by molecular inversion probe technology (MIP), SNP6, or 850k methylation array hybridization. Prognostic impact was evaluated in 120 patients with follow-up data from the HIT2000 medulloblastoma trial or HIT registries...

BACKGROUND: Split-hand/ foot malformation with long bone deficiency 3 (SHFLD3) is an extremely rare condition associated with duplications located on 17p13.3, which invariably encompasses the BHLHA9 gene. The disease inherits with variable expressivity and significant incomplete penetrance as high as 50%. RESULTS: We have detected 17p13.3 locus one-allele triplication in a male proband from family 1 (F1.1), and duplication in a male proband from family 2 (F2.1) applying array comparative genomic hybridization (array CGH)...

OBJECTIVE: To investigate the expression level of vascular endothelial growth factor (VEGF) in serum of patients with multiple myeloma (MM) and its possible clinical significance. METHODS: 68 patients with MM who were admitted to The First Affiliated Hospital of Bengbu Medical College from July 2019 to June 2020 were collected. The expression level of VEGF was detected by VEGF enzyme-linked immunosorbent assay, the correlation of VEGF expression with serous effusion in MM was explored, and the relationship between VEGF expression level and clinical features and prognosis of patients with MM was analyzed...

OBJECTIVE: Compared to European, Japanese, and Chinese populations, genetic studies on intracranial aneurysms (IAs) in Koreans are lacking. We conducted an updated genome-wide association study (GWAS) to more accurately identify candidate variations predicting IA by genotype correction and imputation than in the first Korean GWAS. METHODS: We performed a high-throughput imputation of single-nucleotide polymorphisms (SNPs) and genotype missing values for 250 IA and 296 controls...

PURPOSE OF REVIEW: An intact DNA damage response is crucial to preventing cancer development, including in myeloid and lymphoid malignancies. Deficiencies in the homologous recombination (HR) pathway can lead to defective DNA damage responses, and this can occur through inherited germline mutations in HR pathway genes, such as CHEK2 and ATM. We now understand that germline mutations can be identified frequently (~ 5-10%) in patients with myeloid and lymphoid malignancies, and among the most common of these are CHEK2 and ATM...

17p13.1-2 microdeletion syndrome is a congenital anomaly syndrome with characteristic facial features and multiple malformations. The prevalence of epilepsy with 17p13.1-2 microdeletion is low, with only one case reported for late-onset spasms. Late-onset spasms is one of the rare epilepsy syndromes and one of the developmental epileptic encephalopathies requiring urgent treatment. We experienced two cases of 17p13.1-2 microdeletion syndrome, one of which presented with epileptic spasms in cluster at 18 months of age...

OBJECTIVE: To present the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS)/PAFAH1B1-related lissencephaly to further determine fetal phenotypes of this syndrome. STUDY DESIGN: This was a retrospective study of ten pregnancies with fetal MDS/PAFAH1B1-related lissencephaly identified by chromosomal microarray (CMA)/exome sequencing (ES). Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, CMA or ES results and pregnancy outcomes...

YWHAE gene is located on chromosome 17p13.3, and its product 14-3-3epsilon protein belongs to 14-3-3 protein family. As a molecular scaffold, YWHAE participates in biological processes such as cell adhesion, cell cycle regulation, signal transduction and malignant transformation, and is closely related to many diseases. Overexpression of YWHAE in breast cancer can increase the ability of proliferation, migration and invasion of breast cancer cells. In gastric cancer, YWHAE acts as a negative regulator of MYC and CDC25B , which reduces their expression and inhibits the proliferation, migration, and invasion of gastric cancer cells, and enhances YWHAE-mediated transactivation of NF-κB through CagA...

BACKGROUND: Selinexor 80 mg combined with low-dose dexamethasone (Sd) demonstrated significant clinical benefit in patients with relapsed/refractory multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a global phase II STORM study. The present study, MARCH, addresses China regulatory needs to further validate the data from STORM in Chinese patients with RRMM. METHODS: The MARCH study was conducted at 17 sites in China, where eligible Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled...

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Chromosome 17p13.3 microduplication syndrome is considered a multisystem disorder that results in a wide variety of clinical manifestations including dysmorphic facial characteristics, brain structural malformations, developmental restriction, growth restriction, and neurocognitive disorders. The two major classes of chromosome 17p13.3 microduplication, which have different clinical presentations, are associated with specific genetic regions. Among the various known phenotypes, scattered cases with congenital heart disease (CHD) have been reported for both classes of chromosome 17p13...

BACKGROUND: Neuroblastoma is rarer in African American (AA) children compared with American children of European descent. AA children affected with neuroblastoma, however, more frequently develop the high-risk form of the disease. METHODS: We have genotyped an AA cohort of 629 neuroblastoma cases (254 high-risk) and 2,990 controls to investigate genetic susceptibility to neuroblastoma in AAs. RESULTS: We confirmed the known neuroblastoma susceptibility gene BARD1 at genome-wide significance in the subset of high-risk cases...

BACKGROUND: African Americans (AA) are substantially underrepresented in Alzheimer's disease (AD) genetic studies, yet their admixed genetic ancestry (African and European) provides a unique opportunity to identify novel genetic factors associated with AD related to genetic ancestry. Admixture mapping (AM) provides a more powerful approach than SNP-based genome-wide association studies (GWAS) in admixed populations in part due to the lower multiple testing burden. In this study we used AM to identify regions associated with AD in AA individuals...

Multiple myeloma (MM) patients with suboptimal response to induction therapy or early relapse, classified as the functional high-risk (FHR) patients, have been shown to have poor outcomes. We evaluated newly-diagnosed MM patients in the CoMMpass dataset and divided them into three groups: genomic high-risk (GHR) group for patients with t(4;14) or t(14;16) or complete loss of functional TP53 (bi-allelic deletion of TP53 or mono-allelic deletion of 17p13 (del17p13) and TP53 mutation) or 1q21 gain and International Staging System (ISS) stage 3; FHR group for patients who had no markers of GHR group but were refractory to induction therapy or had early relapse within 12 months; and standard-risk (SR) group for patients who did not fulfill any of the criteria for GHR or FHR...

BACKGROUND: Children with 17p13.3 microdeletions including the YWHAE gene show intrauterine growth restriction, craniofacial dysmorphisms, postnatal growth failure, and cognitive impairment. This region is characterized by genomic instability and has been associated with isolated lissencephaly sequence and Miller-Dieker syndrome characterized by facial dysmorphisms, microcephaly, short stature, seizures, cardiac malformations, and agyria. Whilst brain abnormalities are secondary to YWHAE deficiency, the cause of pre- and postnatal growth failure has not been identified yet...

Hyperdiploid multiple myeloma (MM) is associated with better prognosis and non-hyperdiploid subtype is associated with variable to adverse prognosis based on the nature of karyotype abnormality.  Rarely exceptions to this hyperdiploid and non-hyperdiploid divisions do exist in a minority. We report an adult male MM patient who showed hyperdiploid karyotype with few novel complex abnormalities and who showed poor clinical outcome. Conventional cytogenetic analysis carried out in 22 GTG banded metaphases showed 53,Y,der(X)t(X;22)(q27;q11...

Spontaneous abortion occurs in 8-20% of recognized pregnancies and usually takes place in the first trimester (7-11 weeks). There are many causes of pregnancy loss, but the most important (about 75%) is the presence of chromosomal aberrations. We present the results of oligonucleotide array application in a cohort of 62 miscarriage cases. The inclusion criteria for the study were the loss after 8th week of pregnancy and the appearance of recurrent miscarriages. DNA was extracted from trophoblast or fetal skin fibroblasts...