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Biological Reviews of the Cambridge... Aug 2017The grey wolf (Canis lupus) is an iconic large carnivore that has increasingly been recognized as an apex predator with intrinsic value and a keystone species. However,... (Meta-Analysis)
Meta-Analysis Review
The grey wolf (Canis lupus) is an iconic large carnivore that has increasingly been recognized as an apex predator with intrinsic value and a keystone species. However, wolves have also long represented a primary source of human-carnivore conflict, which has led to long-term persecution of wolves, resulting in a significant decrease in their numbers, genetic diversity and gene flow between populations. For more effective protection and management of wolf populations in Europe, robust scientific evidence is crucial. This review serves as an analytical summary of the main findings from wolf population genetic studies in Europe, covering major studies from the 'pre-genomic era' and the first insights of the 'genomics era'. We analyse, summarize and discuss findings derived from analyses of three compartments of the mammalian genome with different inheritance modes: maternal (mitochondrial DNA), paternal (Y chromosome) and biparental [autosomal microsatellites and single nucleotide polymorphisms (SNPs)]. To describe large-scale trends and patterns of genetic variation in European wolf populations, we conducted a meta-analysis based on the results of previous microsatellite studies and also included new data, covering all 19 European countries for which wolf genetic information is available: Norway, Sweden, Finland, Estonia, Latvia, Lithuania, Poland, Czech Republic, Slovakia, Germany, Belarus, Russia, Italy, Croatia, Bulgaria, Bosnia and Herzegovina, Greece, Spain and Portugal. We compared different indices of genetic diversity in wolf populations and found a significant spatial trend in heterozygosity across Europe from south-west (lowest genetic diversity) to north-east (highest). The range of spatial autocorrelation calculated on the basis of three characteristics of genetic diversity was 650-850 km, suggesting that the genetic diversity of a given wolf population can be influenced by populations up to 850 km away. As an important outcome of this synthesis, we discuss the most pressing issues threatening wolf populations in Europe, highlight important gaps in current knowledge, suggest solutions to overcome these limitations, and provide recommendations for science-based wolf conservation and management at regional and Europe-wide scales.
Topics: Animals; Conservation of Natural Resources; Europe; Genetic Variation; Genetics, Population; Microsatellite Repeats; Wolves
PubMed: 27682639
DOI: 10.1111/brv.12298 -
International Journal of Molecular... Jan 2024Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
Topics: Humans; Cardiomyopathy, Hypertrophic; Genetic Testing; Arrhythmias, Cardiac; Autopsy; Fibrosis; Phenotype; Death, Sudden, Cardiac
PubMed: 38279275
DOI: 10.3390/ijms25021275 -
Journal of Neurology May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by...
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is characterised by early onset stroke and dementia. Most strokes are lacunar ischaemic strokes, but intracerebral haemorrhage (ICH) has also been reported, although there are limited published data on its frequency and characteristics.
METHODS
A retrospective review of a prospectively recruited CADASIL register from the British National Referral clinic was performed to identify acute ICH cases and their characteristics. In addition, a systematic review of ICH in CADASIL was performed. MEDLINE (Pubmed), Embase, and Web of Science were searched for articles published from inception until 31/05/2023.
RESULTS
Ten cases of ICH were identified from the National clinic register of 516 symptomatic patients, giving an estimated point prevalence of 1.9%. An additional 119 cases were identified from the systematic review, comprising 129 cases and 142 ICH events in total. Including all identified cases, the mean age at onset of ICH was 56.6 ± 15.7 (SD) years, and 74 (57.4%) were male. ICH was the first manifestation of the disease in 32 patients (38.1%), and ICH recurrence occurred in 16 (12.4%). Most ICHs were subcortical, with the thalamus, 58 (40.8%), and basal ganglia, 34 (23.9%), being the commonest sites. Anticoagulation, but not antiplatelet agents, was associated with an increased risk of ICH (20.0% vs. 1.9%, p = 0.006).
CONCLUSIONS
ICH is a relatively rare manifestation of CADASIL, occurring in about 2% of symptomatic cases. Most of the haemorrhages occurred in the subcortical regions.
Topics: Humans; CADASIL; Cerebral Hemorrhage; Middle Aged; Male; Prevalence; Risk Factors; Female; Aged; Adult; Retrospective Studies
PubMed: 38217707
DOI: 10.1007/s00415-023-12177-0 -
PloS One 2013Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid ('premature aging') syndrome which is associated with an elevated risk of cancer. (Review)
Review
BACKGROUND
Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid ('premature aging') syndrome which is associated with an elevated risk of cancer.
OBJECTIVES
Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population.
METHODS
We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates.
RESULTS
We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia.
CONCLUSIONS
WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.
Topics: Humans; Incidence; Japan; Neoplasms; Risk; Werner Syndrome
PubMed: 23573208
DOI: 10.1371/journal.pone.0059709 -
Neurological Sciences : Official... Mar 2023Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of HSP can extend to include other neurologic features, including movement disorders. Our aim was to investigate genotype-phenotype associations in HSP with a focus on movement disorders.
METHODS
We performed a systematic review and individual participant data (IPD)-level meta-analysis by retrieving publications from Medline/EMBASE/Web of Science on HSP with a SPG genotype. Studies were included only if individual-level information was accessible and at least one patient with a movement disorder was reported for that genotype. Out of 21,957 hits, 192 manuscripts with a total of 1413 HSP cases were eligible. Data were compared between two HSP groups: manifested with (HSP-MD, n = 767) or without (HSP-nMD, n = 646) a movement disorder.
RESULTS
The HSP-MD group had an older age of onset (20.5 ± 16.0 vs. 17.1 ± 14.2 yr, p < 0.001) and less frequent autosomal dominant inheritance (7.6% vs. 30.1%, p < 0.001) compared to HSP-nMD. SPG7 (31.2%) and SPG11 (23.8%) were the most frequent genotypes in the HSP-MD group. HSP-MD with SPG7 had higher frequency of later onset during adulthood (82.9% vs. 8.5%), ataxia (OR = 12.6), extraocular movement disturbances (OR = 3.4) and seizure (OR = 3.7) compared to HSP-MD with SPG11. Conversely, SPG11 mutations were more frequently associated with consanguinity (OR = 4.1), parkinsonism (OR = 7.8), dystonia (OR = 5.4), peripheral neuropathy (OR = 26.9), and cognitive dysfunction (OR = 34.5).
CONCLUSION
This systematic IPD-level meta-analysis provides the largest data on genotype-phenotype associations in HSP-MD. Several clinically relevant phenotypic differences were found between various genotypes, which can possibly facilitate diagnosis in resource-limited settings.
Topics: Humans; Spastic Paraplegia, Hereditary; Paraplegia; Mutation; Movement Disorders; Phenotype; Proteins
PubMed: 36441344
DOI: 10.1007/s10072-022-06516-8 -
Child's Nervous System : ChNS :... Feb 2021Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities... (Review)
Review
Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.
Topics: Acrocephalosyndactylia; Brain; Craniosynostoses; Facial Bones; Humans; Hydrocephalus
PubMed: 33083874
DOI: 10.1007/s00381-020-04934-7 -
Frontiers in Neurology 2021Cerebral small vessel disease (SVD) is a common cause of stroke, mild cognitive impairment, dementia and physical impairments. Differences in SVD incidence or severity...
Cerebral small vessel disease (SVD) is a common cause of stroke, mild cognitive impairment, dementia and physical impairments. Differences in SVD incidence or severity between males and females are unknown. We assessed sex differences in SVD by assessing the male-to-female ratio (M:F) of recruited participants and incidence of SVD, risk factor presence, distribution, and severity of SVD features. We assessed four recent systematic reviews on SVD and performed a supplementary search of MEDLINE to identify studies reporting M:F ratio in covert, stroke, or cognitive SVD presentations (registered protocol: CRD42020193995). We meta-analyzed differences in sex ratios across time, countries, SVD severity and presentations, age and risk factors for SVD. Amongst 123 relevant studies ( = 36,910 participants) including 53 community-based, 67 hospital-based and three mixed studies published between 1989 and 2020, more males were recruited in hospital-based than in community-based studies [M:F = 1.16 (0.70) vs. M:F = 0.79 (0.35), respectively; < 0.001]. More males had moderate to severe SVD [M:F = 1.08 (0.81) vs. M:F = 0.82 (0.47) in healthy to mild SVD; < 0.001], and stroke presentations where M:F was 1.67 (0.53). M:F did not differ for recent (2015-2020) vs. pre-2015 publications, by geographical region, or age. There were insufficient sex-stratified data to explore M:F and risk factors for SVD. Our results highlight differences in male-to-female ratios in SVD severity and amongst those presenting with stroke that have important clinical and translational implications. Future SVD research should report participant demographics, risk factors and outcomes separately for males and females. [PROSPERO], identifier [CRD42020193995].
PubMed: 34777227
DOI: 10.3389/fneur.2021.756887 -
The American Journal of Gastroenterology Jun 2010Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with increased cancer risk. Surveillance and patient management are, however,... (Review)
Review
OBJECTIVES
Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder associated with increased cancer risk. Surveillance and patient management are, however, hampered by a wide range in cancer risk estimates. We therefore performed a systematic review to assess cancer risks in PJS patients and used these data to develop a surveillance recommendation.
METHODS
A systematic PubMed search was performed up to February 2009, and all original articles dealing with PJS patients with confirmed cancer diagnoses were included. Data involving cancer frequencies, mean ages at cancer diagnosis, relative risks (RRs), and cumulative risks were collected.
RESULTS
Twenty-one original articles, 20 cohort studies, and one meta-analysis fulfilled the inclusion criteria. The cohort studies showed some overlap in the patient population and included a total of 1,644 patients; 349 of them developed 384 malignancies at an average age of 42 years. The most common malignancy was colorectal cancer, followed by breast, small bowel, gastric, and pancreatic cancers. The reported lifetime risk for any cancer varied between 37 and 93%, with RRs ranging from 9.9 to 18 in comparison with the general population. Age-related cumulative risks were given for any cancer and gastrointestinal, gynecological, colorectal, pancreatic, and lung cancers.
CONCLUSIONS
PJS patients are markedly at risk for several malignancies, in particular gastrointestinal cancers and breast cancer. On the basis of these elevated risks, a surveillance recommendation is developed to detect malignancies in an early phase and to remove polyps that may be premalignant and may cause complications, so as to improve the outcome.
Topics: Adolescent; Adult; Aged; Breast Neoplasms; Child; Digestive System Neoplasms; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Neoplasms; Peutz-Jeghers Syndrome; Population Surveillance; Risk Factors; Young Adult
PubMed: 20051941
DOI: 10.1038/ajg.2009.725 -
Hormone Research in Paediatrics 2023Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions.
OBJECTIVES
This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH.
METHODS
PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types.
RESULTS
This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient.
CONCLUSIONS
This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Neonatal Screening; Adrenal Cortex; Mutation; Steroid 21-Hydroxylase
PubMed: 35973409
DOI: 10.1159/000526401 -
Indian Journal of Nephrology 2021The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the gene. The syndrome is characterized by impaired... (Review)
Review
The enamel renal syndrome (ERS) is a rare autosomal recessive disease that is associated with mutations in the gene. The syndrome is characterized by impaired amelogenesis of the hypoplastic type and nephrocalcinosis, presenting with presence of thin or absence of enamel, late dental eruption, intrapulpal calcifications, bilateral nephrocalcinosis, and normal plasma calcium level. The objective is to characterize ERS by systematically literature reviewing, highlighting the main findings of the syndrome to increase knowledge about this condition in the health professionals. The study is a systematic review of the scientific literature, whose research was developed in the PubMed database in March 2018. A total of 69 articles were found. Two authors analyzed their abstracts and selected, according to the language and main subject, 30 articles to write this study. A total of 69 patients were cited in the studies and their data were analysed. There was gender equivalence and the ages ranged from 1 to 64 years old. There is a clear hereditary relation of the syndrome, since there was consanguinity in 18 cases, indicating a percentage of 26.08% and family history in 30 cases (43.47%). Laboratory changes vary greatly from patient to patient and may even remain unchanged. The relationship between the syndrome and the mutation in the gene can be proven from the data, since all patients with ERS screened by the mutation were positive. With the advancement of the ERS studies, some associations with the syndrome are suspected, such as the presence of gingival fibromatosis, hearing loss, and hypertrichosis. Thus, it is noticed that the syndrome does not show a predilection for gender or age and there is a strong hereditary character, marked by the consanguinity and family history of the patients. The association with the gene is reinforced, since the mutation was identified in all patients analyzed.
PubMed: 33994680
DOI: 10.4103/ijn.IJN_27_19