The cover image based on Original Article Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites by Christine C. Bruels, DOI: 10.1002/mgg3.552.

In this paper, is reported the identification of two chimeric patients, a rare finding if sexual abnormalities are absent. However, their chimeric condition is responsible at least for the Silver–Russell phenotype observed in one of the two patients. By single nucleotide polymorphism-array analyses, it was possible to clearly define the mechanism responsible for this unusual finding, underlining the importance of this technique in bringing out the perhaps submerged world of chimeras.

DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35y and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing. DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial-risk women who were noncarriers, but occurs at earlier age. We found only one case of DCIS raised in BRCA1 carrier which had same pathological feature with independently and simultaneously occurred invasive cancer of triple negative. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER-positive, PR-positive, and lower proliferation.

In conclusion, colorectal cancer (CRC) patients were presented with different immune repertoire in comparison with healthy controls. In this study, significant difference in TRBV and TRBJ gene usage in between case and control group could provide some potential bio-marker for the diagnosis and the treatment of the patients with CRC.

Our data suggested that miR-186 contribute to the pathogenesis of COPD, and the miR-186 may also affect the HIF-1α-dependent lung structure maintenance program.

Clinical genetic testing with deep next-generation sequencing of 166 specimens from 80 patients with suspected mosaic overgrowth conditions resulting a 45%–61% diagnostic yield and was highly influenced by the tissue submitted and phenotype. Three prenatal cases illustrate remaining challenges in prenatal diagnosis of mosaic overgrowth syndromes.

Hearing impairment is one of most frequent birth defects. Here, we have investigated the molecular etiology of non-syndromic deafness patients in Shanxi Province, which has the highest frequency of birth defects in China. In our research, it was found that c.235delC in GJB2 and c.919-2A>G (IVS7-2A>G) in SLC26A4 were the highest frequency pathogenic variants in Shanxi Province. Taken together, our data will enrich the database of deafness mutations and will help clinical diagnosis, treatment, and genetic counseling of hearing impairment.

Autosomal recessive congenital ichthyosis (ARCI) is a phenotypically and genetically heterogeneous skin disease, associated with defects in the skin permeability barrier. Here, we have detected mutations in the genes TGM1, ABCA12, CYP4F22, NIPAL4, and ALOXE3 in 19 consanguineous families from Saudi Arabia, Yemen, and Pakistan. Our results revealed new insights into genotype/phenotype correlations and contribute to expanding the mutational spectrum of ARCI.

There is no significant correlation between frequency of genotypes for rs56103835 among the healthy and patient population. It was found that the TT genotype increased the age of the disease as compared to other genotypes.

In a maternal inherited family, bilateral striatal necrosis was associated with homoplasmic mitochondrial 3697G>A mutation that resulted in an isolated defect of complex I. Although no possible modifier genes on the X chromosome were found, male offspring presented with severe spastic dystonia and complete penetrance, but the female offspring showed mild symptom and low penetrance.

In this paper, we evaluated whether genetic polymorphisms in IL1-R1 and 1L1-R2 genes are associated with the risk of HAPE in Chinese Han population, and the result suggested that IL1-R2 polymorphisms may contribute to the protection of HAPE.

This study aimed to explore whether FAM13A polymorphisms influenced the liver cirrhosis risk. We analyzed the expression of the FAM13A gene in liver cirrhosis tissues by immunohistochemistry. The relationship between FAM13A gene polymorphism and liver cirrhosis was studied by association analysis. Our findings demonstrated that the high expression of FAM13A was associated with an increased risk of liver cirrhosis.

The human leukocyte antigens-DQB2 rs7453920 GA genotype was related to a considerably increased risk of tuberculosis (TB). However, AA genotype was not related to an increased risk of TB.

This study demonstrates that this cfDNA prenatal screening assay, QNatal^® Advanced^™, provides highly accurate discrimination between affected and unaffected pregnancies among a population of pregnant women at average or high risk for fetal genetic abnormalities. This has significant implications for patient care in the general obstetrical population. Increased understanding of assay performance facilitates improved clinical care and appropriate medical management for all patients.

We reported a patient with TBK1 mutation p.Ile334Thr and identify its potential disturbance of neuroinflammatory pathway in vitro.

Altered expression of miR-200a and miR-204 in differentiated PC12 cells in response to MPP⁺, suggested that deregulation of them participates in MPP+ neurotoxicity mechanisms, possibly via affecting the expression of Sirt1 and BCL2 as potential targets.

We analyzed array comparative genomic hybridization (aCGH) data from 47 individuals with intestinal malrotation and identified six rare copy number variants (CNVs), of which five involved known syndrome loci. Two of the known syndromes (Cornelia de Lange type 5 and 18q terminal deletion syndrome) have not previously been associated with intestinal malrotation.

The aim of this study was to investigate the association between genetic polymorphisms in RTEL1 gene and CHD risk, and these findings demonstrated that the genetic variants of RTEL1 may contribute to a protective role against CHD risk.

We developed a novel bioinformatics pipeline to identify potentially aberrant novel essential splice site (PANESS) mutations in next-generation sequencing data, and used it successfully to identify a pathogenic splice site mutation in ATP2A1 for a family with a myotonic phenotype. The pathogenic nature of the mutation was confirmed via RT-PCR, western blot, and immunohistochemistry, along with functional studies in Drosophila.

This is so far the most comprehensive evidence-based meta-analysis on rs2046210 polymorphism and individual susceptibility to BC. Our findings indicated that rs2046210 polymorphism may serve as a potential genetic biomarker of BC in both Asians and Caucasians.

Forkhead box O3 (FOXO3) exhibited positive activities on the proliferation and doxorubicin resistance in colon cancer (CC) cells via targeting MDR1.

The prevalence of DICER1 pathogenic variants was 1:4,600 in The Cancer Genome Atlas (TCGA). The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.

This manuscript addresses the growing need to assign cancer risk to rare variants of uncertain significance. In this manuscript, we have described a proband with a personal history of early-onset renal and thyroid cancers, and a family history of renal and other cancers. Our data suggest the possibility of risk associated with interaction of two or more reported variants and provides the basis for analysis in other families.

Our study aimed to explore whether IL1-R1/IL1-R2 polymorphisms influenced ONFH risk, the study indicated that the rs11674595 (IL-1R2), rs10490571, and rs3917225 (IL-1R1) were significantly associated with increased the risk of ONFH in the Chinese Han population.

A boy was born with perineal hypospadias, a micropenis and cryptorchidism. An interstitial deletion on chromosome 8's short arm (46, XY, del (8)(p23.1p23.1)) is likely to explain the genital abnormalities since GATA4 and SOX7 genes were deleted. After reviewing the literature, we conclude that a 8p deletion should be searched for also in isolated 46XY DSD cases.

Majority of osteogenesis imperfecta cases have de novo nature. Out of studied 146 collagen-related osteogenesis imperfecta patients from Estonia, Ukraine and Vietnam, 56% harbored de novo mutations. de novo and inherited osteogenesis imperfecta patients differed in phenotype severity and mutational spectrum.

We describe the identification of a diagnostic EXT1 gene fusion in a patient with multiple osteochondromas following extensive negative clinical testing. Follow up reanalysis of clinical results revealed an underlying mosaic chromosomal deletion. The article reveals shortcomings in clinical testing and is the first report of a gene fusion diagnostic of multiple osteochondromas.

we found a new mutation site and pathogenic mechanism of the lamp2 gene. Our work illustrates the power of applying WES to identify gene mutations in genetic disorders.

This is the first study to systematically evaluate the contribution of TRPV5 (a calcium channel-related gene) tag-SNPs to Blood lead levels in lead-related occupational workers. In this study, we treated the BLL as a continuous variable and performed a multiple linear regression instead of the logistic regression in traditional case-control study. We successfully indentified that a noble TRPV5 polymorphism rs4252424 is significantly associated with the individuals’ BLL. The following expression quantitative trait loci analysis (eQTL) also highlighted the remarkable protective effect of rs4252424 CT genotype in persons underwent the same external exposure of plumbum.

rs2243283 in the IL-4 gene was potentially associated with an increased risk of steroid-induced ONFH. We also observed a protective effect of rs2243289 in the dominant model.

Single-optical molecule mapping (SMOM) was investigated as a new tool for the molecular diagnosis of FSHD1. Benchmarking against gold standard Sothern blot hybridization and FISH combing, SMOM analysis of a five-generation FSHD1 pedigree, correctly identified the founding 4qA disease-causing allele with a shortened D4Z4 array of 4 repeat units and the corresponding nondisease 4qB allele.

Transient receptor potential cation channel subfamily V member 4 (TRPV4) is an ion channel permeable to Ca²⁺ that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. The novel c.2401A>G (p.K801E) variant of TRPV4 is described using protein informatics, molecular modeling, genomic exome analysis, and clinical study to confirm the pathogenicity for the variant.

Summarized the current research on PAX1 gene methylation in cancer screening. PAX1 gene methylation is a promising biomarker in cervical cancer. Proposed combine HPV test and PAX1 methylation analysis in cervical cancer accurate screening.

Unmet medical needs of individuals with Prader–Willi syndrome make it a rare disease that models the importance of multidisciplinary approaches to care with collaboration between academic centers, medical homes, industry, and parent organizations. Establishment of centers motivates collaboration of experts to provide evidence-based new standards of care, increases the knowledge base regarding success of treatments through randomized controlled trials, and offers an additional resource for patient and family concerns.

This is the first case of male patient showing early seizure type of Rett-like phenotypes by a missense variant on MECP2.

The GBA gene is important in Parkinson's and Gaucher disease, but difficult to sequence due to a highly homologous adjacent pseudogene. Here we present a novel method using long reads on the Oxford Nanopore MinION, which can detect missense mutations and an exonic deletion, with the added advantage of phasing and intronic analysis.