Abstract:
:Current practice by clinical diagnostic laboratories is to utilize online prediction programs to help determine the significance of novel variants in a given gene sequence. However, these programs vary widely in their methods and ability to correctly predict the pathogenicity of a given sequence change. The performance of 17 publicly available pathogenicity prediction programs was assayed using a dataset consisting of 122 credibly pathogenic and benign variants in genes associated with the RASopathy family of disorders and limb-girdle muscular dystrophy. Performance metrics were compared between the programs to determine the most accurate program for loss-of-function and gain-of-function mechanisms. No one program correctly predicted the pathogenicity of all variants analyzed. A major hindrance to the analysis was the lack of output from a significant portion of the programs. The best performer was MutPred, which had a weighted accuracy of 82.6% in the full dataset. Surprisingly, combining the results of the top three programs did not increase the ability to predict pathogenicity over the top performer alone. As the increasing number of sequence changes in larger datasets will require interpretation, the current study demonstrates that extreme caution must be taken when reporting pathogenicity based on statistical online protein prediction programs in the absence of functional studies.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Walters-Sen LC,Hashimoto S,Thrush DL,Reshmi S,Gastier-Foster JM,Astbury C,Pyatt REdoi
10.1002/mgg3.116subject
Has Abstractpub_date
2015-03-01 00:00:00pages
99-110issue
2issn
2324-9269journal_volume
3pub_type
杂志文章abstract:BACKGROUND:Resources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not alway...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1397
更新日期:2020-10-01 00:00:00
abstract:BACKGROUND:Chromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.507
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:A family with skeletal and craniofacial anomalies is presented. Whole-exome sequencing (WES) analysis indicated a diagnosis of Larsen syndrome, although their clinical presentation does not include the hallmark joint dislocations typically observed in Larsen syndrome. METHODS:Patient consent for the sharing...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.648
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Deletional hereditary persistence of fetal hemoglobin (HPFH)/δβ-thalassemia and δ-thalassemia are rare inherited disorders which may complicate the diagnosis of β-thalassemia. The aim of this study was to reveal the frequency of these two disorders in Southwestern China. METHODS:A total of 33,596 subjects w...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.706
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:Incontinentia pigmenti (IP) is a rare X-linked disorder affecting the skin and other ectodermal tissues that is caused by mutation of the IKBKG/NEMO gene. Previous studies have reported that the overall mutation detection rate in IP is ~75%. We hypothesized that a low-level mosaicism existed in the remaining...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1531
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Ankylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase-3 (MMP3) in the development of AS has few been investigated in Chinese population. METHODS:A total of 362 patients ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.752
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:The dreadful prognosis of nonmuscle invasive bladder cancer mainly results from the delay in recognition of individuals with a high risk of progression. Thus, the emphasis of this work lies in developing valuable biomarkers that is conducive to accurately predicting the progression of NMIBC. METHODS:Microar...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.982
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Preeclampsia (PE) is a pregnancy-related hypertensive disorder, which may stem from impair placentation. Renin-angiotensin system is one of the mediators of decidualization and trophoblastic proliferation. In the present study women with PE were studied in a comparison of normotensive controls to determine w...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.799
更新日期:2019-07-01 00:00:00
abstract::Medical genetics and genomic medicine in Turkey: a bright future at a new era in life sciences. ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.326
更新日期:2017-09-03 00:00:00
abstract:BACKGROUND:CAP+1 [A>C] (HBB:c.-50A>C) is a rare silent β-thalassemia (β-thal) mutation. Carrier individuals of this mutation show borderline hemoglobin (Hb), mean corpuscular volume (MCV) and Hb A2 levels. This mutation was previously reported in combination with different β-thalassemia mutations, leading to variable p...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1602
更新日期:2021-01-24 00:00:00
abstract:BACKGROUND:Congenital disorder of glycosylation (CDG) type I is a group of rare disorders caused by recessive mutations in up to 25 genes that impair the N-glycan precursor formation and its transfer to proteins resulting in hypoglycosylation of multiple proteins. Congenital disorder of glycosylation causes multisystem...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1304
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsisten...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.527
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM# 617140) syndrome is a rare, autosomal dominant genetic disorder caused by heterozygous variants in the SON gene (OMIM#182465, GenBank#NC_000021.9). There are only 33 cases and 26 causative SON variants reported to date since the first report in 2015. Here, we report a n...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1496
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:This study set out to determine key lncRNAs correlated with sepsis via constructing competing endogenous RNA (ceRNA) network. METHODS:Three septic patients and three healthy controls were recruited to obtain lncRNA profiles in this current study. Combined with the mRNA profiles by RNA-sequencing, an integra...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1557
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:With the implementation of a research project providing whole genome sequencing (WGS) to all pediatric cancer patients in Denmark (2016-2019), we sought to investigate healthcare professionals' views on WGS as it was actively being implemented in pediatric oncology. METHODS:Semistructured interviews were ca...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1276
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:Cervical cancer as one of the most common malignant tumors lead to bad prognosis among women. Some researches already focus on the carcinogenesis and pathogenesis of cervical cancer, but it is still necessary to identify more key genes and pathways. METHODS:Differentially expressed genes were identified by ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1200
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:Studies evaluating next-generation sequencing (NGS) for retinal disorders may not reflect clinical practice. We report results of retrospective analysis of patients referred for clinical testing at two institutions (US and India). METHODS:This retrospective study of 131 patients who underwent clinically val...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1081
更新日期:2020-02-01 00:00:00
abstract::In this letter, we want to add information to the paper "Genetics and genomic medicine in Argentina" that we considered it was lacking. Argentina is a big country with inequalities in the access to public health care, especially in medical genetics and genomics. ...
journal_title:Molecular genetics & genomic medicine
pub_type: 评论,信件
doi:10.1002/mgg3.571
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.11...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.728
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5-1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of rem...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.466
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:Age-related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1218
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:As a common malignant tumor in the colon, colon cancer (CC) has high incidence and recurrence rates. This study is designed to build a prognostic model for CC. METHODS:The gene expression dataset, microRNA-seq dataset, copy number variation (CNV) dataset, DNA methylation dataset, and transcription factor (T...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1255
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Neural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes. Here, we report the correlation between histone lysine malonylation in diabetes...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1403
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cance...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.402
更新日期:2018-04-17 00:00:00
abstract:BACKGROUND:Male-specifically inherited Y-STRs have been widely used in population genetics and forensic investigations. METHODS:We genotyped and analyzed Y chromosome haplotypes of 408 unrelated Tibeto-Burman-speaking Yi male individuals from Guizhou using Goldeneye® Y-PLUS kit. Population comparisons between the Guiz...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1572
更新日期:2021-01-15 00:00:00
abstract:BACKGROUND:Submicroscopic chromosomal imbalance is associated with an increased nuchal translucency (NT). Most previous research has recommended the use of chromosomal microarray analysis (CMA) for prenatal diagnosis if the NT ≥ 3.5 mm. However, there is no current global consensus on the cutoff value for CMA. In this ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.811
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Persistently high levels of phenylalanine lead to irreversible damage to the nervo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1559
更新日期:2021-01-19 00:00:00
abstract::We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region betw...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.146
更新日期:2015-07-01 00:00:00
abstract:BACKGROUND:Milroy-like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF-C variations found in a female proband b...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1389
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:To search for new prevention markers for early detection of the diseases caused by tobacco, we aimed to investigate the polymorphisms in TSLP and TSLPRs associated with cigarette smoking in the Saudi population. MATERIALS AND METHODS:Samples were collected from 177 smokers and 126 healthy controls. Three TS...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.842
更新日期:2019-08-01 00:00:00