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Clinical Neurology and Neurosurgery Nov 2020Despite numerous reports in syndromic gliomas, the underlying genetic and molecular basis of familial, non-syndromic gliomas, in first degree relatives, remains unclear.... (Review)
Review
OBJECTIVE
Despite numerous reports in syndromic gliomas, the underlying genetic and molecular basis of familial, non-syndromic gliomas, in first degree relatives, remains unclear. This rare cohort of patients harboring invasive primary brain tumors with poor prognosis may provide a potential substrate of understanding the complex genetic cascade triggering tumorigenesis.
METHODS
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 and The Cochrane Handbook of Systematic Reviews of Interventions. PubMed/MEDLINE, Embase and CENTRAL databases were accessed with set inclusion and exclusion criteria.
RESULTS
Following returns of 6756 articles, systematic analysis resulted in 48 papers, with 18 case series, 4 linkage analysis, 3 case-control studies, 1 cohort study, and 22 case reports. A total of 164 first degree relatives of 72 families were analyzed. The most common genetic alterations associated with non-syndromic familial gliomas reported to affect chromosomes 17 (51.1 % germline and 9.3 % tumor mutations), 22 (15.6 % germline and 6 % tumor mutations) and 1 and 19 (4.4 % germline and 9.3 % tumor mutations), with the most commonly affected genes TP53 (8.5 %) and NF2 (3.7 %). Tumor suppressors or cell-cycle regulators, cell signaling and transcription regulation or methylation were the most common gene function categories.
CONCLUSION
Four specific chromosomes (17, 22, 1 and 19) and two specific genes (TP53 and NF2) appear to be most commonly involved. This appears to be the first systematic review of genetic factors underlying non-syndromic glioma clustering in families. The defined list of genetic abnormalities, linked to familial gliomas, may facilitate therapeutic targets and future treatment design.
Topics: Brain Neoplasms; Case-Control Studies; Cell Transformation, Neoplastic; Cohort Studies; Glioma; Humans; Mutation; Pedigree
PubMed: 33039851
DOI: 10.1016/j.clineuro.2020.106222 -
The Journal of Clinical Endocrinology... Aug 2015Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother... (Review)
Review
CONTEXT
Pregnancies complicated by a pheochromocytoma or paraganglioma are very rare, being estimated to occur in 0.007% of all pregnancies. Both the well-being of the mother and fetus need to be considered, and management can be challenging. The optimal management of women with a pheochromocytoma or paraganglioma in pregnancy is not well established.
OBJECTIVE
The objective of the study was to assess whether there is a difference in fetal or maternal mortality between pheochromocytomas and paragangliomas in pregnancy.
DESIGN
We present an experience of eight pregnancies in four SDHB germline mutation-positive women with sympathetic paragangliomas, followed by a systematic review of the literature to compare the outcome of paragangliomas with that of pheochromocytomas occurring in pregnancy.
RESULTS
In our case series, favorable fetal and maternal outcomes were seen in all eight pregnancies. From the systematic review, maternal and fetal mortality were lower in women with paragangliomas, at 3.6% and 12% respectively, compared with 9.8% and 16% in women with pheochromocytomas.
CONCLUSION
Pregnant women with paragangliomas may be at a lower risk of adverse outcome than those with pheochromocytomas, but both maternal and fetal mortality rates are still higher than that of the general obstetric population.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Female; Humans; Paraganglioma; Pedigree; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Siblings; Young Adult
PubMed: 26083822
DOI: 10.1210/jc.2015-2122 -
Otology & Neurotology : Official... Jan 2019To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, and propose an up-to-date classification of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To describe the genetic and phenotypic spectrum of Usher syndrome after 6 years of studies by next-generation sequencing, and propose an up-to-date classification of Usher genes in patients with both visual and hearing impairments suggesting Usher syndrome, and in patients with seemingly isolated deafness.
STUDY DESIGN
The systematic review and meta-analysis protocol was based on Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed 1) a meta-analysis of data from 11 next-generation sequencing studies in 684 patients with Usher syndrome; 2) a meta-analysis of data from 21 next-generation studies in 2,476 patients with seemingly isolated deafness, to assess the involvement of Usher genes in seemingly nonsyndromic hearing loss, and thus the proportion of patients at high risk of subsequent retinitis pigmentosa (RP); 3) a statistical analysis of differences between parts 1) and 2).
RESULTS
In patients with both visual and hearing impairments, the biallelic disease-causing mutation rate was assessed for each Usher gene to propose a classification by frequency: USH2A: 50% (341/684) of patients, MYO7A: 21% (144/684), CDH23: 6% (39/684), ADGRV1: 5% (35/684), PCDH15: 3% (21/684), USH1C: 2% (17/684), CLRN1: 2% (14/684), USH1G: 1% (9/684), WHRN: 0.4% (3/684), PDZD7 0.1% (1/684), CIB2 (0/684). In patients with seemingly isolated sensorineural deafness, 7.5% had disease-causing mutations in Usher genes, and are therefore at high risk of developing RP. These new findings provide evidence that usherome dysfunction is the second cause of genetic sensorineural hearing loss after connexin dysfunction.
CONCLUSION
These results promote generalization of early molecular screening for Usher syndrome in deaf children.
Topics: High-Throughput Nucleotide Sequencing; Humans; Mutation; Pedigree; Usher Syndromes
PubMed: 30531642
DOI: 10.1097/MAO.0000000000002054 -
European Journal of Neurology Mar 2022Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to...
BACKGROUND
Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece.
METHODS
After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece.
RESULTS
We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations).
CONCLUSIONS
The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.
Topics: Adult; Aged; CADASIL; Greece; Humans; Magnetic Resonance Imaging; Middle Aged; Mutation; Receptor, Notch3; Receptors, Notch; Young Adult
PubMed: 34761493
DOI: 10.1111/ene.15180 -
Ophthalmic Genetics Apr 2023Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries...
BACKGROUND
Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries and populations, these therapies may not be efficacious in East Asians.
MATERIALS AND METHODS
A literature search was conducted from 1966 to September 2022 for cohort studies on East Asian populations reporting on non-syndromic RP genotypes and variants. Population-weighted prevalence was used to determine the genotypes and individual variants across the entire cohort. The carrier prevalence of common variants was compared against those in Europe.
RESULTS
A total of 12 articles describing 2,932 clinically diagnosed East Asian RP probands were included. We identified 876 variants across 54 genes. The most common genotypes included USH2A, EYS, RPGR, ABCA4, PRPF31, RHO, RP1, RP2, PDE6B and SNRNP200, with USH2A as the most common (17.1%). Overall, 60.5% of probands with clinically relevant variants were found to have one of the genotypes above, with 543/876 (62.0%) of the variants occurring in these genes. The most frequently reported variant was USH2A missense variant c.2802T>G/p.C934W (4.9%). Carrier prevalence of these variants was significantly different ( < 0.0001) than in Europe.
CONCLUSIONS
USH2A was the most commonly affected RP gene in this East Asian cohort, although sub-population analysis revealed distinct genotype prevalence patterns. While the genotypes are similar between East Asia and European cohorts, variants are specific to East Asia. The identification of several prevalent variants in USH2A and EYS provides an opportunity for the development of therapeutics that are relevant for East Asia patients.
Topics: Humans; DNA Mutational Analysis; East Asian People; Genotype; Mutation; Pedigree; Retinitis Pigmentosa; Extracellular Matrix Proteins
PubMed: 36856324
DOI: 10.1080/13816810.2023.2182329 -
Frontiers in Plant Science 2021Faba bean is a cool-season grain legume crop, which is grown worldwide for food and feed. Despite a decrease in area under faba bean in the past, the interest in growing...
Faba bean is a cool-season grain legume crop, which is grown worldwide for food and feed. Despite a decrease in area under faba bean in the past, the interest in growing faba bean is increasing globally due to its high seed protein content and its excellent ecological service. The crop is, however, exposed to diverse biotic and abiotic stresses causing unstable, low grain yield. Although, sources of resistance to main diseases, such as ascochyta blight ( Speg.), rust ( (Pers.) Schroet.), chocolate spot ( Sard.) and gall disease (), have been identified, their resistance is only partial and cannot prevent grain yield losses without agronomical practices. Tightly associated DNA markers for host plant resistance genes are needed to enhance the level of resistance. Less progress has been made for abiotic stresses. Different breeding methods are proposed, but until now line breeding, based on the pedigree method, is the dominant practice in breeding programs. Nonetheless, the low seed multiplication coefficient and the requirement for growing under insect-proof enclosures to avoid outcrossing hampers breeding, along with the lack of tools such as double haploid system and cytoplasmic male sterility. This reduces breeding population size and speed of breeding hence the chances of capturing rare combinations of favorable alleles. Availability and use of the DNA markers such as vicine-convicine ( ) and herbicide tolerance in breeding programs have encouraged breeders and given confidence in marker assisted selection. Closely linked QTL for several biotic and abiotic stress tolerance are available and their verification and conversion in breeder friendly platform will enhance the selection process. Recently, genomic selection and speed breeding techniques together with genomics have come within reach to accelerate the genetic gains in faba bean. Advancements in genomic resources with other breeding tools, methods and platforms will enable to accelerate the breeding process for enhancing genetic gain in this species.
PubMed: 34721470
DOI: 10.3389/fpls.2021.744259 -
BJU International Oct 2017Active surveillance (AS) is an increasingly prevalent treatment choice for low grade prostate cancer. Eligibility criteria for AS are varied and it is unclear if family... (Meta-Analysis)
Meta-Analysis Review
Active surveillance (AS) is an increasingly prevalent treatment choice for low grade prostate cancer. Eligibility criteria for AS are varied and it is unclear if family history of prostate cancer should be used as an exclusion criterion when considering men for AS. To determine whether family history plays a significant role in the progression of prostate cancer for men undergoing active surveillance, PubMed searches of 'family history and prostate cancer', 'family history and prostate cancer progression' and 'factors of prostate cancer progression' were used to identify research publications about the relationship between family history and prostate cancer progression. These searches generated 536 papers that were screened and reviewed. Six publications were ultimately included in this analysis. Review of the six publications suggests that family history does not increase the risk of prostate cancer progression, whilst a subgroup analysis in one study found that family history increases the risk of prostate cancer progression only in African-Americans. A family history of prostate cancer does not appear to increase a patient's risk of having more aggressive prostate cancer and is therefore unlikely to be an important factor in determining eligibility for AS. Further studies are needed to better understand the relationship between race, family history, and eligibility for AS.
Topics: Aged; Early Detection of Cancer; Genetic Predisposition to Disease; Humans; Incidence; Male; Middle Aged; Observational Studies as Topic; Patient Selection; Pedigree; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; United States; Watchful Waiting
PubMed: 28371016
DOI: 10.1111/bju.13862 -
Pediatric Surgery International Aug 2014The co-occurrence of Hirschsprung's disease (HSCR) and multiple endocrine neoplasia type 2 (MEN2) is a relatively rare event. The basis for this association is the... (Review)
Review
PURPOSE
The co-occurrence of Hirschsprung's disease (HSCR) and multiple endocrine neoplasia type 2 (MEN2) is a relatively rare event. The basis for this association is the presence of a "Janus" mutation in the RET proto-oncogene--a mutation that acts simultaneously as both a gain-in-function and a loss-of-function mutation. To date, four mutations in the exon 10 region of RET that are known to cause MEN2A have been implicated in this association: C620, C618, C611 and C609. We performed a systematic review of the published literature on this association to determine its incidence, the prevalence and phenotype of HSCR associated with the 4 RET mutations mentioned above.
METHODS
A systematic literature-based search for relevant articles was conducted using three online databases. After exclusion of ineligible publications, we recorded data on all patients with a diagnosis of HSCR or MEN2A with a "Janus" RET mutation, as well as those who carried the mutation but were unaffected. Statistical analysis was performed using SPSS.
RESULTS
The literature search yielded 885 publications, of which 36 articles, incorporating data on 341 individuals, were eligible for inclusion in the final analysis. Co-occurrence of HSCR and MEN2A was recorded in 84 cases (24.6 %). HSCR occurred alone in 64 carriers of a "Janus" mutation (18.8 %) and MEN2A occurred in isolation in 173 cases (50.7 %). Twenty individuals (5.9 %) were found to carry a "Janus" mutation after screening on the basis of family history but were unaffected by either MEN2A or HSCR. The most common mutation recorded was the C620 mutation [114 cases (48.1 %)]. There was a relatively high incidence of long-segment aganglionosis (29.3 %) and total colonic aganglionosis (17.3 %) in this cohort. This trend was particularly notable in those with C620 mutations, only 33 % of whom had short-segment disease.
CONCLUSION
While the overall incidence of HSCR co-occurring with MEN2A is low, both conditions occur with a relatively high frequency in families with a RET mutation at exon 10. The proportion of cases of long-segment HSCR and total colonic aganglionosis is higher than that in the general population with HSCR in those with C620 and C618 mutations. These findings reinforce the importance of RET mutation testing in HSCR when a family history of either HSCR or MEN2 is present. In families with MEN2A and known exon 10 RET mutations, the threshold for investigation for HSCR in those with gastrointestinal symptoms should be very low. High-quality prospective longitudinal studies of large HSCR populations are required to shed greater light on this rare but important phenomenon.
Topics: Child; DNA Mutational Analysis; DNA, Neoplasm; Hirschsprung Disease; Humans; Multiple Endocrine Neoplasia Type 2a; Mutation; Pedigree; Phenotype; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret
PubMed: 24972642
DOI: 10.1007/s00383-014-3538-2 -
Journal of Current Ophthalmology 2023To look for causative genetic mutations in a series of Iranian families with strabismus. In addition, we systematically reviewed all the published articles regarding the... (Review)
Review
Role of Abelson Helper Integration Site 1, Nebulin, and Paired Box 3 Genes in the Development of Nonsyndromic Strabismus in a Series of Iranian Families: Sequence Analysis and Systematic Review of the Genetics of Nonsyndromic Strabismus.
PURPOSE
To look for causative genetic mutations in a series of Iranian families with strabismus. In addition, we systematically reviewed all the published articles regarding the role of genetic variations in primary and nonsyndromic comitant strabismus.
METHODS
Four families with a history of multiple cases of primary and nonsyndromic comitant strabismus were enrolled in this study. Polymerase chain reaction and Sanger sequencing of exons 23, 11, and 3 of the Abelson helper integration site 1 (), nebulin (), and paired box 3 () genes were performed, respectively. One offspring of a consanguineous marriage underwent whole-exome sequencing (WES) to look for possible causative variants. To conduct a systematic review, we thoroughly searched PubMed, Scopus, and ISI Web of Knowledge extracting relevant publications, released by April 2021.
RESULTS
We examined four Iranian strabismus pedigrees with multiple affected offspring in different generations. Among these 17 participants, 10 family members had strabismus and 7 were healthy. Sanger sequencing did not reveal a causative mutation. Therefore, to further investigate, one affected offspring was chosen for WES. The WES study demonstrated two possible variants in and genes. These genetic variants showed high allele frequency in our population and are thought to be polymorphisms in our series of Iranian families.
CONCLUSIONS
We demonstrated that mutations in , , and genes were not common in a series of Iranian patients with familial strabismus. Moreover, by performing WES, we revealed that two variants of uncertain significance as possible causative variants for strabismus are not related to this disease in our population.
PubMed: 38681684
DOI: 10.4103/joco.joco_53_22 -
PloS One 2022To systematically review the relationship between genotypes and clinical phenotypes of Familial exudative vitreoretinopathy (FEVR) to support risk estimation and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically review the relationship between genotypes and clinical phenotypes of Familial exudative vitreoretinopathy (FEVR) to support risk estimation and therapeutic decisions.
DESIGN
Systematic review with meta-analysis.
DATA SOURCES
The data of our study were collected from PubMed, Embase, Web of Science, Cochrane, CBM, China National Knowledge Infrastructure (CNKI), WAN FANG and VIP databases since inception to August 2021.
RESULTS
A total of 3257 patients from 32 studies were included according to the inclusion and exclusion criteria. Among all the cases, the mutation frequencies of LRP5, FZD4, NDP, TSPAN12, ZNF408 and KIF11 were 13.6%, 11.5%, 4.6%, 6.7%, 1.6%, and 5.7%, respectively. We found that the patients with NDP and FZD4 suffer more severe symptoms, among which 86.4% patients of NDP and 78.6% patients of FZD4 were in the advanced stage of FEVR. Retinal detachment is the most frequent symptom with patients of LRP5 and NDP mutations, accounting for 51.9% and 64.5%, respectively. For the patients with the mutation of TSPAN12, retinal fold is the most common clinical manifestation, and suffer the mildest clinical phenotypes compared with the other three genes.
CONCLUSION
The results of the meta-analysis indicate that different types of genetic mutations occur at different frequencies. In addition, the clinical manifestations of FEVR are related to the type of gene mutation. Therefore, targeted treatment strategies and follow-up recommendations should be adopted for different pathogenic genes of FEVR.
Topics: DNA Mutational Analysis; DNA-Binding Proteins; Eye Diseases, Hereditary; Familial Exudative Vitreoretinopathies; Frizzled Receptors; Genetic Association Studies; Humans; Low Density Lipoprotein Receptor-Related Protein-5; Mutation; Pedigree; Retinal Diseases; Tetraspanins; Transcription Factors
PubMed: 35830446
DOI: 10.1371/journal.pone.0271326