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 validated targeted NGS or exome sequencing for a wide variety of clinical phenotypes categorized results into a definitive, indeterminate, or negative molecular diagnosis. RESULTS:A definitive molecular diagnosis (52%) was more common in the India cohort (62% vs. 39%, p = .009), while an indeterminate molecular diagnosis occurred only in the US cohort (12%). In the US cohort, a lower diagnostic rate in Hispanic, non-Caucasians (23%) was seen compared to Caucasians (57%). The India cohort had a high rate of homozygous variants (61%) and different frequency of genes involved compared to the US cohort. CONCLUSION:Despite inherent limitations in clinical testing, the diagnostic rate across the two cohorts (52%) was similar to the 50%-65% diagnostic rate in the literature. However, the diagnostic rate was lower in the US cohort and appears partly explained by racial background. The high rate of consanguinity in the Indian population is reflected in the high rate of homozygosity for pathogenic mutations and may have implications for population level screening and genetic counseling. Clinical laboratories may note diagnostic rates that differ from the literature, due to factors such as heterogeneity in racial background or consanguinity rates in the populations being tested. This information may be useful for post-test counseling.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Yohe S,Sivasankar M,Ghosh A,Ghosh A,Holle J,Murugan S,Gupta R,Schimmenti LA,Vedam R,Thyagarajan Bdoi
10.1002/mgg3.1081subject
Has Abstractpub_date
2020-02-01 00:00:00pages
e1081issue
2issn
2324-9269journal_volume
8pub_type
杂志文章abstract:PURPOSE:To assess clinical chromosomal microarray (CMA) genomic testing reports for the following: (a) usage of reporting elements consistent with 2011 ACMG guidelines and other elements identified in the primary literature, (b) information quality, and (c) readability. METHODS:We retrospectively analyzed genomic test...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.551
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) has high fatality and permanent disability rates due to the severe damage to brain cells and inflammation. The SERPINE1 gene that encodes PAI-1 for the regulation of tissue plasminogen activator is considered an important therapeutic target for aSAH. METHODS:Six SNP...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.737
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations. METHODS:We describe a 6-year-old child with a 12-Mb deletion of the region 7q35q36.3. RESULTS:Amo...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.855
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MBSHH , MBWNT , MBGroup 3 , and MBGroup 4 , representing the second most common type of pediatric brain cancer after high-grade gliomas. They suffer from a high prevalence of genetic predispositio...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1302
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:HNF1A gene regulates liver-specific genes, and genes that have a role in glucose metabolism, transport, and secretion of insulin. HNF1A gene mutations are frequently associated with type 2 diabetes. HNF1A protein has three domains: the dimerization domain, the DNA-binding domain, and the trans-activation dom...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.261
更新日期:2016-11-30 00:00:00
abstract:BACKGROUND:Achondroplasia (ACH), the most common form of short-limbed skeletal dysplasia, is caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. More than 97% of patients result from a heterozygous p.G380R mutation in the FGFR3 gene. We present here a child who had two de novo ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1148
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:The NIPAL4 gene is described to be implicated of Congenital Ichthyosiform Erythroderma (CIE). It encodes a magnesium transporter membrane-associated protein, hypothetically involved in epidermal lipid processing and in lamellar body formation. The aim of this work is to investigate the causative mutation in ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1104
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:The heritability of several psychiatric disorders is high, and specific at-risk variants have been identified. Therefore, genetic counseling and genetic testing can be prescribed to some psychiatric patients, but these services are not standardized for most of the population. The aims of the study were to ga...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.830
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:The protein NgR1 is encoded by RTN4R, a gene linked to schizophrenia. We previously reported NgR1 as receptor for the epilepsy-linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation. Impairments in synapse formation a...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.215
更新日期:2016-03-11 00:00:00
abstract:BACKGROUND:Over 500 epigenetic regulators have been identified throughout the human genome. Of these, approximately 30 chromatin modifiers have been implicated thus far in human disease. Recently, variants in BRPF1, encoding a chromatin reader, have been associated with a previously unrecognized autosomal dominant synd...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.665
更新日期:2019-06-01 00:00:00
abstract::The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.4
更新日期:2013-05-01 00:00:00
abstract:BACKGROUND:Copy number variants in coding and noncoding genomic regions have been implicated as risk factor for schizophrenia (SCZ). Rare duplications of the RB1CC1 gene were found enriched in SCZ patients. Considering that the effect of such duplications on RB1CC1 expression has never been evaluated and partial gene d...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1561
更新日期:2020-12-19 00:00:00
abstract::Single mutations in the ATP-binding cassette transporter (ABCC6) gene (OMIM 603234) are known to cause the rare autosomal recessive disease pseudoxanthoma elasticum (PXE). Recently, we have found that copy number variations (CNVs) in pseudogenes of the ABCC6 gene are quite common. The aim of this study was to investig...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.137
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND:Primary microcephaly (MCPH) is a congenital neurodevelopmental disorder manifesting as small brain and intellectual disability. It underlies isolated reduction of the cerebral cortex that is reminiscent of early hominids which makes it suitable model disease to study the hominin-specific volumetric expansion...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1408
更新日期:2020-09-01 00:00:00
abstract::Point mutations in intronic regions near mRNA splice junctions can affect the splicing process. To identify novel splicing variants from exome sequencing data, we developed a bioinformatics splice-site prediction procedure to analyze next-generation sequencing (NGS) data (SpliceFinder). SpliceFinder integrates two fun...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.23
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protei...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1566
更新日期:2020-12-11 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:Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease with colorectal adenomatous polyps as the main clinical manifestations. The objective of this study was to analyze and compare the expression levels of tumor proliferation and angiogenesis-related genes in different tissue secti...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1534
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Obesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. I...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1113
更新日期:2020-03-01 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: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: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:22q11 deletion syndrome (22qDS) is caused by deletion of chromosome region 22q11.2. However, mosaic cases with 22q11.2 deletion syndrome (22q11.2DS) are rarely reported. METHODS:Chromosomal microarray analysis (CMA) and fluorescence in situ hybridization fluorescence in situ hybridization (FISH) were perfor...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.847
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Very recently, compound heterozygous loss-of-function mutations in TELO2 were shown to underlie the newly-described You-Hoover-Fong syndrome. TELO2 forms part of the co-chaperone triple T complex (TTT complex), which plays an important role in the maturation and stabilization of the phosphatidylinositol 3-ki...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.287
更新日期:2017-07-28 00:00:00
abstract:BACKGROUND:Historically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies. METHODS:Two approaches, hospital and community...
journal_title:Molecular genetics & genomic medicine
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/mgg3.443
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:Bicuspid aortic valve (BAV) is the most common congenital heart defect with a prevalence of 1%-2% in the general population. NOTCH1, SMAD6, and GATA5 are associated with BAV in humans, but few cases have been reported that did not involve NOTCH1. Here, we identified novel in-frame variants in SMAD6 (c.1168_1...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.620
更新日期:2019-05-01 00:00:00
abstract:PURPOSE:Histone deacetylase inhibitor (HDACI) is a novel therapeutic option for cancer. However, the effects of HDACIs on chronic myeloid leukemia (CML) and the underlying mechanisms are still unknown. The aim of this study was to investigate the effect and the mechanism-of-action of two HDACI members, sodium butyrate ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.613
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Pre-mRNA splicing is a complex process requiring the identification of donor site, acceptor site, and branch point site with an adjacent polypyrimidine tract sequence. Splicing is regulated by splicing regulatory elements (SREs) with both enhancer and suppressor functions. Variants located in exonic regions ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.840
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molec...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1539
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Fanconi anemia (FA) affects only one in 130,000 births, but has severe and diverse clinical consequences. It has been theorized that defects in the FA DNA cross-link repair complex lead to a spectrum of variants that are responsible for those diverse clinical phenotypes. METHODS:Using NextGen sequencing, we...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.502
更新日期:2018-11-01 00:00:00