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The Journal of Craniofacial SurgeryIntracranial epidermoid cyst (EC) and craniofacial fibrous dysplasia (CFD) were histogenetically different rare congenital benign diseases. The coexistence of...
OBJECTIVES
Intracranial epidermoid cyst (EC) and craniofacial fibrous dysplasia (CFD) were histogenetically different rare congenital benign diseases. The coexistence of intracranial EC and CFD was extremely rare and had not been reported yet.
MATERIALS AND METHODS
We retrospectively reviewed the clinical and radiologic information of 3 patients diagnosed with concomitant EC and CFD at Beijing Tiantan Hospital from January 2003 to January 2021 and summarized their clinicopathological features, treatment modalities, and outcomes. In addition, we performed a systematic review of cases of the coexisting intracranial EC and other intracranial abnormalities to explore the potential connections.
RESULTS
There were 2 women and 1 man with the mean age of 31 years old. Satisfactory resection was fulfilled for all the 3 ECs. CFD, however, was managed with watchful waiting. During the mean follow-up time of 58 months, all the ECs showed no sign of recurrence, and all the CFD lesions remained stable. Two EC specimens underwent genetic study, showing no GNAS mutations and negative G s α protein expression. In the literature review of concomitant intracranial EC and other intracranial abnormalities, 23 studies were included. With 5 reported cases, the intracranial aneurysm was found to be the most common intracranial disease that coexisted with EC.
CONCLUSIONS
The coexistence of intracranial EC and CFD was extremely rare. However, no convincing mechanism and evidence underlying such coexistence had been found. To provide more profound understanding about these 2 diseases and improve diagnosis and treatment strategy, further research and verification should be considered.
Topics: Male; Humans; Female; Adult; Dermoid Cyst; Retrospective Studies; Fibrous Dysplasia of Bone
PubMed: 36727926
DOI: 10.1097/SCS.0000000000009166 -
Journal of Clinical Neurology (Seoul,... Apr 2021Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of... (Review)
Review
BACKGROUND AND PURPOSE
Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset.
METHODS
We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including 'spinocerebellar ataxia' and several synonyms of 'preataxic manifestation'. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers.
RESULTS
We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament light-chain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers.
CONCLUSIONS
Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.
PubMed: 33835738
DOI: 10.3988/jcn.2021.17.2.187 -
The World Journal of Men's Health Jan 2023Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize...
PURPOSE
Globozoospermia is a genetic syndrome characterized by the presence of round-headed spermatozoa and infertility due to the inability of these spermatozoa to fertilize the oocyte. In this article, we present the clinical case of a young globozoospermic patient with a new, not yet described mutation of the gene. We also performed a systematic review of the literature on gene mutations, the outcome of assisted reproductive techniques, and the risk of transmission of abnormalities to the offspring in patients with globozoospermia and made recommendations to offer a more appropriate clinical management of these patients.
MATERIALS AND METHODS
We performed a systematic search in the PubMed, Google Scholar, and Scopus databases from their inception to December 2021. The search strategy included the combination of the following Medical Subjects Headings (MeSH) terms and keywords: "globozoospermia", "round-headed spermatozoa", "round head spermatozoa", "intracytoplasmic sperm injection", "ICSI", "offspring", "child health", "assisted reproductive technique outcome". All the eligible studies were selected following the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model. The quality of included studies was assessed by applying the "Cambridge Quality Checklists".
RESULTS
The main genes involved in the pathogenesis of globozoospermia are , , , , , , , and genes. Other genes could also play a role. These include , , , , , , and . Globozoospermic patients should undergo ART to achieve fertility. In particular, intracytoplasmic sperm injection with assisted oocyte activation or intracytoplasmic morphologically-selected sperm injection appears to be associated with a higher success rate. Patients with globozoospermia should also be evaluated for the high rate of sperm aneuploidy which appears to influence the success rate of ART but does not appear to be associated with an increased risk of transmission of genetic abnormalities to offspring.
CONCLUSIONS
This systematic review summarizes the evidence on the gene panel to be evaluated, ICSI outcomes, and the health of the offspring in patients with globozoospermia. Evidence-based recommendations on the management of patients with globozoospermia are provided.
PubMed: 36047070
DOI: 10.5534/wjmh.220020 -
Molecular Genetics and Genomics : MGG Sep 2022Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited...
Disorders that result from de-arrangement of growth, development and/or differentiation of the appendages (limbs and digit) are collectively called as inherited abnormalities of human appendicular skeleton. The bones of appendicular skeleton have central role in locomotion and movement. The different types of appendicular skeletal abnormalities are well described in the report of "Nosology and Classification of Genetic skeletal disorders: 2019 Revision". In the current article, we intend to present the embryology, developmental pathways, disorders and the molecular genetics of the appendicular skeletal malformations. We mainly focused on the polydactyly, syndactyly, brachydactyly, split-hand-foot malformation and clubfoot disorders. To our knowledge, only nine genes of polydactyly, five genes of split-hand-foot malformation, nine genes for syndactyly, eight genes for brachydactyly and only single gene for clubfoot have been identified to be involved in disease pathophysiology. The current molecular genetic data will help life sciences researchers working on the rare skeletal disorders. Moreover, the aim of present systematic review is to gather the published knowledge on molecular genetics of appendicular skeleton, which would help in genetic counseling and molecular diagnosis.
Topics: Brachydactyly; Clubfoot; Humans; Limb Deformities, Congenital; Molecular Biology; Polydactyly; Syndactyly
PubMed: 35907958
DOI: 10.1007/s00438-022-01930-1 -
Pediatric Dermatology Mar 2021Nevus comedonicus (NC) syndrome is a condition first identified in 1978. The cause of NC syndrome has been recently proven to be a gain-of-function, mosaic postzygotic... (Review)
Review
Nevus comedonicus (NC) syndrome is a condition first identified in 1978. The cause of NC syndrome has been recently proven to be a gain-of-function, mosaic postzygotic mutation of the NEK9 gene. A systematic review of the literature retrieved 43 well-established cases of NC syndrome reported so far. Three morphological variants of NC in NC syndrome emerged: (a) the more common, predominantly comedonal type; (b) "Selhorst type"; and (c) "atrophoderma vermiculatum" type. NC syndrome is mainly associated with ocular, skeletal, and neural abnormalities, most typically ipsilateral congenital cataract and malformations of fingers and toes.
Topics: Humans; NIMA-Related Kinases; Nevus; Pigmentation Disorders; Skin Neoplasms; Syndrome; Toes
PubMed: 33481271
DOI: 10.1111/pde.14508 -
International Journal of Gynecological... Dec 2023Endometrial cancers with more than one molecular feature- mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)-are called 'multiple...
BACKGROUND
Endometrial cancers with more than one molecular feature- mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)-are called 'multiple classifiers'.
OBJECTIVE
To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them.
METHODS
Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification.
RESULTS
Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%.
CONCLUSIONS
The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and sequencing.
PubMed: 38135437
DOI: 10.1136/ijgc-2023-004864 -
International Journal of Gynaecology... Jul 2022The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd),... (Review)
Review
BACKGROUND
The TCGA molecular groups of endometrial carcinoma are "POLE-mutated" (POLEmut), "microsatellite-instable/mismatch repair-deficient" (MSI/MMRd), "TP53-mutated/p53-abnormal" (TP53mut/p53abn), and "no specific molecular profile" (NSMP).
OBJECTIVE
Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS).
SEARCH STRATEGY
Systematic review from January 2000 to January 2021.
SELECTION CRITERIA
Studies assessing the TCGA groups in UCS.
DATA COLLECTION AND ANALYSIS
Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P < 0.050.
MAIN RESULTS
Five studies with 263 UCS were included. Compared with TP53mut/p53abn UCS, MSI/MMRd UCS showed significantly better PFS (P < 0.001) but similar OS (P = 0.788), whereas NSMP UCS showed similar PFS (P = 0.936) and OS (P = 0.240). Compared with their endometrioid/serous counterparts, NSMP and TP53mut/p53abn UCS showed significantly worse PFS (P < 0.001 and P = 0.004) and OS (P < 0.001 and P < 0.001), while MSI/MMRd UCS showed similar PFS (P = 0.595) but significantly worse OS (P < 0.001). The POLEmut group showed neither recurrences nor deaths in both the UCS and the endometrioid/serous carcinoma cohorts.
CONCLUSION
POLEmut UCS show excellent prognosis, whereas TP53mut/p53abn and NSMP UCS show a prognosis even worse than that of TP53mut/p53abn endometrioid/serous carcinomas. The prognosis of MSI/MMRd UCS remains to be defined.
Topics: Carcinoma, Endometrioid; Carcinosarcoma; Endometrial Neoplasms; Female; Humans; Prognosis; Uterine Neoplasms
PubMed: 34536971
DOI: 10.1002/ijgo.13937 -
Journal of Ophthalmology 2022Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive... (Review)
Review
OBJECTIVES
Alport syndrome (AS) is a severe, rare hereditary disorder that can lead to end-stage renal disease, auditory degeneration, and ocular abnormalities. Despite extensive research on AS in relation to auditory and renal disorders, more research is needed on the ocular presentations of AS. This systematic review aims to summarize the common ocular abnormalities in patients with AS and to explore the potential treatment options for these irregularities.
METHODS
The PubMed, MEDLINE, and EMBASE databases were systematically searched from January 1977 to April 2022. Only papers that were published in the English language and explored the ocular abnormalities in AS patients were selected. We manually searched reference lists of included papers for additional studies.
RESULTS
A total of 23 articles involving 195 patients were included in this review. The common ocular manifestations in AS patients are lenticonus, macular holes, fleck retinopathy, and thinning of the macula. Although published literature has described the use of cataract surgeries and vitrectomies as standard surgical techniques to alleviate ocular abnormalities in non-AS patients, it must be noted that surgical techniques have not been evaluated in a large research study as a solution for AS abnormalities. Another prospective treatment for AS is gene therapy through the reversion of causative variants to wild type or exon-skipping therapy for -linked AS with truncating mutations. Gene therapy, however, remains unable to treat alterations that occur in the fetal and early development phase of the disease.
CONCLUSIONS
The review found no definitive conclusions regarding the efficacy and safety of surgical techniques and gene therapy in AS patients. Recognition of ocular abnormalities through an ophthalmic examination with an optical coherence tomography (OCT) and slit-lamp examination is critical to the medical field, as ophthalmologists can aid nephrologists and other physicians in diagnosing AS. Early diagnosis and care can minimize the risk of detrimental ocular outcomes, such as blindness and retinal detachment.
PubMed: 36119140
DOI: 10.1155/2022/9250367 -
Journal of the American Society of... Nov 2023Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the...
SIGNIFICANCE STATEMENT
Several recent studies identified mitochondrial mutations in patients with Gitelman or Fanconi syndrome. Mitochondrial cytopathies are generally not considered in the diagnostic workup of patients with electrolyte disorders. In this systematic review, we investigated the presence of electrolyte disorders in patients with mitochondrial cytopathies to determine the relevance of mitochondrial mutation screening in this population. Our analysis demonstrates that electrolyte disorders are commonly reported in mitochondrial cytopathies, often as presenting symptoms. Consequently, more clinical attention should be raised for mitochondrial disease as cause for disturbances in electrolyte homeostasis. Further prospective cohort studies are required to determine the exact prevalence of electrolyte disorders in mitochondrial cytopathies.
BACKGROUND
Electrolyte reabsorption in the kidney has a high energy demand. Proximal and distal tubular epithelial cells have a high mitochondrial density for energy release. Recently, electrolyte disorders have been reported as the primary presentation of some mitochondrial cytopathies. However, the prevalence and the pathophysiology of electrolyte disturbances in mitochondrial disease are unknown. Therefore, we systematically investigated electrolyte disorders in patients with mitochondrial cytopathies.
METHODS
We searched PubMed, Embase, and Google Scholar for articles on genetically confirmed mitochondrial disease in patients for whom at least one electrolyte is reported. Patients with a known second genetic anomaly were excluded. We evaluated 214 case series and reports (362 patients) as well as nine observational studies. Joanna Briggs Institute criteria were used to evaluate the quality of included studies.
RESULTS
Of 362 reported patients, 289 had an electrolyte disorder, with it being the presenting or main symptom in 38 patients. The average number of different electrolyte abnormalities per patient ranged from 2.4 to 1.0, depending on genotype. Patients with mitochondrial DNA structural variants seemed most affected. Reported pathophysiologic mechanisms included renal tubulopathies and hormonal, gastrointestinal, and iatrogenic causes.
CONCLUSIONS
Mitochondrial diseases should be considered in the evaluation of unexplained electrolyte disorders. Furthermore, clinicians should be aware of electrolyte abnormalities in patients with mitochondrial disease.
Topics: Humans; Mitochondrial Myopathies; Kearns-Sayre Syndrome; Mitochondrial Diseases; Mitochondria; DNA, Mitochondrial; Water-Electrolyte Imbalance
PubMed: 37678265
DOI: 10.1681/ASN.0000000000000224 -
Pathology, Research and Practice Feb 2023Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous studies have indicated that the aberrant expression of LINC00963 is extensively present in various human tumors, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. In this meta-analysis, data from diverse malignancies were analyzed to determine whether LINC00963 expression levels were associated with clinical prognosis and immune infiltration in pan-cancer.
MATERIALS AND METHODS
The eligible studies were identified from several electronic databases from the inception to July 2022 through systematic research. LINC00963 expression and survival were estimated using pooled odds ratios and hazard ratios with 95% CI. We used the Kaplan-Meier method and COX analysis for survival analysis. In addition, Spearman's correlation analysis was used to uncover any correlation between LINC00963 and microsatellites instability (MSI), tumor mutational burden (TMB), DNA methyltransferases (DNMTs), immune checkpoint biomarkers, and the related genes of mismatch repair (MMR).
RESULTS
Our findings indicated that overexpression of LINC00963 was related to poor overall survival (OS) (HR =1.32, 95% CI, 1.09-1.59, P = 0.004). The TCGA database also found that abnormal expression of LINC00963 was linked to overall survival in various cancers. Moreover, there is an association between LINC00963 expression and MSI, TMB, and MMR in malignancies of various types.
CONCLUSION
The results of this study indicate that LINC00963 may serve as a prognostic biomarker and a therapeutic target for cancer. By using it, cancer diagnoses can be improved, treatment targets discovered, and prognostic questions improved.
Topics: Humans; RNA, Long Noncoding; Neoplasms; Prognosis; Survival Analysis; Biomarkers, Tumor
PubMed: 36696806
DOI: 10.1016/j.prp.2022.154291