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Cytogenetic and Genome Research 2015Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of... (Review)
Review
Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be unambiguously identified by banding cytogenetics. The objective of this study was to provide an overview of sSMC frequency and characterization in a context of infertility and to review the literature describing sSMC in relation with male and female infertility. Therefore, a systematic literature review on sSMC associated with infertility was conducted by means of a PubMed literature and a sSMC database (http://ssmc-tl.com/sSMC.html) search. A total of 234 patients with infertility were identified as carriers of sSMC. All chromosomes, except chromosomes 10, 19 and the X, were involved in sSMC, and in 72% the sSMC originated from acrocentric chromosomes. Euchromatic imbalances were caused by the presence of sSMC in 30% of the cases. Putative genes have been identified in only 1.2% of sSMC associated with infertility. The implication of sSMC in infertility could be due to a partial trisomy of some genes but also to mechanical effects perturbing meiosis. Further precise molecular and interphase-architecture studies on sSMC are needed in the future to characterize the relationship between this chromosomal anomaly and human infertility.
Topics: Adult; Chromosome Aberrations; Chromosome Disorders; Female; Genetic Predisposition to Disease; Humans; Infertility, Female; Infertility, Male; Inheritance Patterns; Male
PubMed: 26398339
DOI: 10.1159/000438718 -
Orphanet Journal of Rare Diseases Aug 2016Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister... (Review)
Review
BACKGROUND
Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister formation after minor mechanical trauma. Level of cleavage in the skin, clinical features with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy and/or gene involved, type(s) of mutation present and sometimes specific mutation(s), allow to define the EB type and subtype. This family of genodermatoses exposes patients to several complications, cutaneous squamous cell carcinoma (cSCC) being the most severe of them.
OBJECTIVE
The aim of this systematic review was to document patients with EB who developed cSCC.
METHODS
A systematic literature search was performed, from inception to March 2014, using Medline, Embase, Cochrane and ClinicalTrials.gov databases. Only articles published in English and French were selected. The diagnosis of EB had to be confirmed by EM and/or IFM and/or mutation analysis, while cSCC had to be confirmed by histological analysis.
RESULTS
Of 167 references in the original search, 69 relevant articles were identified, representing 117 cases. cSCCs were identified in all types of EB, though predominantly in recessive dystrophic EB (RDEB) forms (81 cases (69.2 %)). The median age at diagnosis was 36 years old (interquartile range (IQR), 27-48 years and range, 6-71 years) for all forms. Of those with measurements in the literature (88 cases (75.2 %)), tumor size was greater than 2 centimeters in 52 cases (59.1 %). The histopathological characteristics were specified in 88 cases (75.2 %) and well-differentiated forms predominated (73.9 %). No conclusion could be drawn on the choice of surgical treatment or the management in advanced forms.
LIMITATIONS
This study was retrospective and statistical analysis was not included due to various biases. This study design did not allow to infer prevalence, nor EB subtype risk for cSCC occurrence.
CONCLUSIONS
Our study correlated with historical data shows that most of the cSCCs occurred in subjects with the RDEB subtype, however reports also show that cSCCs can present in any patients with EB. The first signs of cSCC developed at a younger age in EB patients than in non-EB patients. Interestingly, the cSCC duration, before its diagnosis, was shorter in individuals with RDEB than with junctional EB (JEB) and dominant dystrophic EB (DDEB). This study further emphasizes the importance of regular monitoring of EB patients, particularly with the RDEB subtype as they developed cSCC at a younger age.
Topics: Carcinoma, Squamous Cell; Epidermolysis Bullosa; Humans; Skin
PubMed: 27544590
DOI: 10.1186/s13023-016-0489-9 -
Cureus Aug 2023Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives... (Review)
Review
Being one of the most prevalent progressive neurodegenerative disorders (falling second only to Alzheimer's disease) with a clinical pattern affecting millions of lives all over the world, Parkinson's disease (PD) has never failed to attract a formidable interest from the vast majority of neurologists and researchers worldwide. This review article will analyze the pathophysiology, etiology, genetics, and pathological stages of Parkinson's disease with their corresponding clinical sequels. A review article was conducted using research databases including PubMed, PubMed Central, Springer, and Elsevier. The research articles reviewed using databases were written in English, German, Japanese, and Chinese and published within the preceding 50 years. Based on the article's findings, we concluded that Parkinson's disease is a progressive disorder with a variety of motor and non-motor symptoms that are influenced by a cascade of pathological neuronal abnormalities such as Lewy neurites and Lewy bodies that gradually build up with an eventual consequence of neurodegeneration of dopamine-secreting neurons. Multiple genetic mutations, pathophysiological events, and environmental factors act as the foundation to initiate that cascade.
PubMed: 37664277
DOI: 10.7759/cureus.44353 -
Scientific Reports Aug 2016Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus... (Review)
Review
Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
Topics: Aged; Biopsy; DNA, Mitochondrial; Female; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondria, Muscle; Mitochondrial Myopathies; Muscle, Skeletal; Mutation; Young Adult
PubMed: 27506553
DOI: 10.1038/srep30610 -
American Journal of Clinical Dermatology Apr 2015Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dystrophic epidermolysis bullosa (DEB), characterized by intense pruritus and hypertrophic, lichenified,... (Review)
Review
INTRODUCTION
Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dystrophic epidermolysis bullosa (DEB), characterized by intense pruritus and hypertrophic, lichenified, prurigo-like papules, plaques, and nodules secondary to scratching. These clinical findings have been attributed to various mutations in the COL7A1 gene. Previous reports have yielded inconsistent findings regarding a possible genotype-phenotype relationship in EBP.
OBJECTIVE
Our aim was to conduct a systematic review aimed at assessing the genotype-phenotype correlation in EBP.
METHODS
A systematic review was conducted using PubMed, Medline, EMBASE, and Cochrane databases for all reports of mutation-verified EBP, published from 1946 to September 2014. Statistical comparison of clinical findings between mutation types was performed using logistic regression analysis.
RESULTS
The review included a total of 28 articles with 74 individuals, which consisted of level 4 non-controlled case series (grade C) and level 5 case reports (grade D). Previous reported mutation types included glycine substitution (GS, 52.7%), in-frame skipping (IFS, 33.8%), non-glycine substitution (NGS, 8.1%), and premature termination codon (PTC, 5.4%). The most common clinical findings were extremities involvement, linear configuration, and nail dystrophy. In comparison with GS mutation carriers, IFS carriers had a higher likelihood of (1) being male (OR 2.99; p = 0.043; 95% CI 1.27-11.4) and (2) presenting with blisters (OR 4.10; p = 0.013; 95% CI 1.34-12.5).
CONCLUSIONS
To our knowledge, this study is the first systematic review examining the relationship between mutation type and clinical presentation in EBP. The findings in this review (1) identify common clinical characteristics of EBP that may help in the assessment of patients with possible EBP; and (2) indicate that certain mutation carriers may have a higher likelihood of exhibiting particular phenotypes. In the case of potential diagnostic challenge, assessment for presence of common clinical findings as well as molecular testing may facilitate correct identification and prognostication.
Topics: Age of Onset; Epidermolysis Bullosa Dystrophica; Genotype; Humans; Mutation; Phenotype
PubMed: 25690953
DOI: 10.1007/s40257-015-0119-7 -
Journal of Vascular Surgery Dec 2016Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect... (Review)
Review
BACKGROUND
Vascular Ehlers-Danlos syndrome (EDS) is a relatively rare genetic syndrome that occurs owing to disorders in the metabolism of fibrillary collagen. These defects affect the soft connective tissues resulting in abnormalities in the skin, joints, hollow organs, and blood vessels. Patients with these defects frequently present at a young age with spontaneous arterial complications involving the medium-sized arteries. Complications involving the hollow organs, such as spontaneous colonic perforation, are observed as well. Given the fragility of the soft tissue, open and endovascular intervention on patients with vascular EDS is fraught with high complication rates.
METHODS
A PubMed search was performed to identify manuscripts published related to vascular EDS. This search included more than 747 articles. These findings were cross-referenced using key terms, including endovascular, embolization, surgery, genetics, pathophysiology, connective tissue disorders, vascular complications, systematic review, type III collagen, and COL3A1.
RESULTS
The references in key articles and review articles were evaluated for additional resources not identified in the PubMed search. Care must be taken to balance the risk of intervention vs the risk of continued observation. Life-threatening hemorrhage, however, mandates intervention.
CONCLUSIONS
With careful, altered approaches to tissue handling, endovascular approaches may provide a safer option for managing the arterial complications observed in patients with vascular EDS. Additional hope may also be found in the use of pharmacologic agents that reduce the incidence and severity of the arterial complications.
Topics: Aneurysm; Collagen Type III; Computed Tomography Angiography; DNA Mutational Analysis; Ehlers-Danlos Syndrome; Endovascular Procedures; Genetic Predisposition to Disease; Humans; Mutation; Phenotype; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 27687326
DOI: 10.1016/j.jvs.2016.06.120 -
BMC Ophthalmology Jul 2016Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major... (Review)
Review
BACKGROUND
Beta-thalassemia is a severe genetic blood disorder caused by a mutation in the gene encoding for the beta chains of hemoglobin. Individuals with beta-thalassemia major require regular lifelong Red Blood Cell transfusions to survive. Ocular involvement is quite common and may have serious implications.
METHODS
Extensive review of observational studies on beta-thalassemia, to determine the prevalence and spectrum of ocular abnormalities, by clinical examination and multimodal imaging, and to investigate risk factors for their development.
RESULTS
Frequency of ocular involvement differs among various studies (41.3-85 %, three studies). Ocular findings in beta-thalassemia may correlate to the disease itself, iron overload or the chelating agents used. Beta-thalassemia ocular manifestations include ocular surface disease, as demonstrated by tear function parameters (two studies). Lens opacities are present in 9.3-44 % (five studies). Lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively (two studies). Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE), including peau d'orange, angioid streaks, pattern dystrophy-like changes, and optic disc drusen are a consistent finding in seven studies. Patients with PXE-like fundus changes were older than patients without these fundus changes (two studies). Age (two studies) and splenectomy (one study) had the strongest association with presence of PXE-like fundus changes. Increased retinal vascular tortuosity independently of the PXE-like fundus changes was found in 11-17.9 % (three studies), which was associated with aspartate amino transferase, hemoglobin and ferritin levels (two studies). Fundus autofluorescence and electrophysiological testing (ERG and EOG) may indicate initial stages or more widespread injury than is suggested by fundus examination (two studies).
CONCLUSIONS
Beta-thalassemia may present with various signs, both structural and functional. Pseudoxanthoma elasticum like fundus changes are a frequent finding in patients with b-thalassemia. These changes increase with duration or severity of the disease. Retinal vascular tortuosity may be an additional disease manifestation related to the severity and duration of anemia and independent of the PXE-like syndrome. Patients with long-standing disease need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.
Topics: Chelating Agents; Humans; Iron Overload; Observational Studies as Topic; Retinal Diseases; Vision Disorders; beta-Thalassemia
PubMed: 27390837
DOI: 10.1186/s12886-016-0285-2 -
Journal of the American Society of... Nov 2014Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families.... (Review)
Review
Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
Topics: Disease Progression; Humans; Kidney; Polycystic Kidney, Autosomal Dominant; Predictive Value of Tests; TRPP Cation Channels
PubMed: 24925719
DOI: 10.1681/ASN.2013111184 -
Ultrasound in Obstetrics & Gynecology :... Apr 2017The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral ventriculomegaly. The aim of this study was to undertake a systematic review and meta-analysis to quantify the perinatal and long-term outcomes in fetuses diagnosed in the second or third trimester of pregnancy with isolated unilateral ventriculomegaly.
METHODS
MEDLINE, EMBASE and The Cochrane Library were searched electronically. Outcomes investigated included incidence of aneuploidy, congenital infection, progression of ventriculomegaly, associated brain and extracerebral abnormalities in the apparently isolated cases and neurodevelopmental delay in both apparently and truly isolated cases. Sensitivity analysis was performed according to whether the ventriculomegaly was mild/moderate (atrial width < 15 mm) or severe (atrial width ≥ 15 mm). Reference lists within relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Meta-analysis of proportions was used, and between-study heterogeneity was assessed using the I test.
RESULTS
The search yielded 2053 citations. The full text was retrieved for 202, and 11 studies were included in the systematic review. In fetuses with apparently isolated unilateral ventriculomegaly, no chromosomal abnormalities were identified and the pooled prevalence of congenital infection was 8.2% (95% CI, 3.6-14.5%). The pooled prevalence of additional brain abnormalities detected prenatally and postnatally by magnetic resonance imaging was 5.1% (95% CI, 0.2-16.1%) and 6.4% (95% CI, 0.3-19.4%), respectively. The pooled prevalence of abnormal neurodevelopment was 5.9% (95% CI, 2.2-11.2%) in apparently isolated cases with an atrial width of < 15 mm, and it was 7.0% (95% CI, 3.2-12.2%) in fetuses with truly isolated unilateral ventriculomegaly. Most cases with apparently isolated ventriculomegaly were classified as mild/moderate (93.5%) and therefore the outcomes in this group were similar to those in the whole cohort of apparently isolated ventriculomegaly.
CONCLUSIONS
The prevalence of aneuploidy, congenital infection and neurodevelopmental delay in fetuses with a prenatal diagnosis of isolated unilateral ventriculomegaly is likely to be low. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Aneuploidy; Congenital Abnormalities; Female; Fetal Diseases; Humans; Hydrocephalus; Infections; Neurodevelopmental Disorders; Perinatal Care; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Ultrasonography, Prenatal
PubMed: 27091707
DOI: 10.1002/uog.15943 -
Clinical Genetics Sep 2023Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process.... (Meta-Analysis)
Meta-Analysis Review
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.
Topics: Humans; Tooth Eruption; Tooth, Unerupted; Core Binding Factor Alpha 1 Subunit; Tooth Abnormalities; Phenotype; Genotype; Chloride Channels
PubMed: 37448157
DOI: 10.1111/cge.14400