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Mashup Score: 1GRN mutation spectrum and genotype–phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort - 2 month(s) ago
Methods The GRN mutations, especially of the loss of function type, are causative of frontotemporal dementia (FTD). However, several GRN variants can be found in other neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease. So far, there have been over 300 GRN mutations reported globally. However, the genetic spectrum and phenotypic characteristics have not been fully elucidated in Chinese population. The participants were from the dementia cohort of Peking Union Medical College Hospital (n=1945). They received history inquiry, cognitive evaluation, brain imaging and exome sequencing. The dementia subjects carrying the rare variants of the GRN were included in this study. Those with the pathogenic or likely pathogenic variants of other dementia-related genes were excluded. Results 14 subjects carried the rare variants of GRN . They were clinically diagnosed with behavioural variant of FTD (n=2), non-fluent/agrammatic variant primary progressive aphasia (PP
Source: jmg.bmj.comCategories: General Medicine News, General Journals & SocietTweet
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Mashup Score: 9Whole-exome sequencing reveals causative genetic variants for several overgrowth syndromes in molecularly negative Beckwith-Wiedemann spectrum - 3 month(s) ago
Background Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations at 11p15. Because approximately 20% of patients test negative via molecular testing of peripheral blood leukocytes, the concept of Beckwith-Wiedemann spectrum (BWSp) was established to encompass a broader cohort with diverse and overlapping phenotypes. The prevalence of other overgrowth syndromes concealed within molecularly negative BWSp remains unexplored. Methods We conducted whole-exome sequencing (WES) on 69 singleton patients exhibiting molecularly negative BWSp. Variants were confirmed by Sanger sequencing or quantitative genomic PCR. We compared BWSp scores and clinical features between groups with classical BWS (cBWS), atypical BWS or isolated lateralised overgrowth (aBWS+ILO) and overgrowth syndromes identified via WES. Results Ten patients, one classified as aBWS and nine as cBWS, showed causative gene variants for Simpson-Golabi-Behmel syndrome (five patients), Sotos sy
Source: jmg.bmj.comCategories: General Medicine News, General Journals & SocietTweet
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Mashup Score: 4
Background Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter. Methods We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia. Results In Europeans, higher genetically predicted TSAT increased genetic liabil
Source: jmg.bmj.comCategories: General Medicine News, General Journals & SocietTweet
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Mashup Score: 1Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel - 10 month(s) ago
Background Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
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Mashup Score: 0A multilayered approach to the analysis of genetic data from individuals with suspected albinism - 10 month(s) ago
Albinism is a clinically and genetically heterogeneous group of conditions characterised by visual abnormalities and variable degrees of hypopigmentation. Multiple studies have demonstrated the clinical utility of genetic investigations in individuals with suspected albinism. Despite this, the variation in the provision of genetic testing for albinism remains significant. One key issue is the…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet-
New paper highlights #albinism, the clinical field where "rare-meets-commmon" disease genetics, requiring multilayered analysis ➡️ clarifies longstanding debate re: impact of TYR c.1205G>A (p.Arg402Gln) OpenAccess: https://t.co/yIxZvLpbLf @ewanbirney @RetinaUK @fightforsightUK https://t.co/W70qTUMCPf
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Mashup Score: 0Evaluation of the clinical, biochemical, genotype and prognosis of mut-type methylmalonic acidemia in 365 Chinese cases - 11 month(s) ago
Background Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase ( mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut -type MMA in Chinese patients. Methods We recruited 365 patients with mut -type MMA; investigated their disease onset, newborn screening…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
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Mashup Score: 1Genotype–phenotype associations in Alström syndrome: a systematic review and meta-analysis - 11 month(s) ago
Background Alström syndrome (ALMS; #203800) is an ultrarare monogenic recessive disease. This syndrome is associated with variants in the ALMS1 gene, which encodes a centrosome-associated protein involved in the regulation of several ciliary and extraciliary processes, such as centrosome cohesion, apoptosis, cell cycle control and receptor trafficking. The type of variant associated with ALMS is…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
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Mashup Score: 0
Background Helios (encoded by IKZF2 ), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4+ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
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Mashup Score: 0Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome - 11 month(s) ago
Background Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS. Methods 1465 individuals with LS (557 MLH1 , 517 MSH2/EPCAM…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
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Mashup Score: 0Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C - 1 year(s) ago
Background RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating leukodystrophy characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease is caused by biallelic pathogenic variants in POLR3A , POLR3B , POLR1C or POLR3K . Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been…
Source: Journal of Medical GeneticsCategories: General Medicine Journals and Societies, Latest HeadlinesTweet
#MarchManuscriptChallenge: ▶️ Explore the genetic spectrum and phenotyes of GRN mutations from the PUMCH dementia cohort 🔎Amnesia was the most prevalent symptom in carriers of rare GRN variants. Just don't forget to check it out! 👀 https://t.co/f9XESbGa4T https://t.co/y5NLM5tjk6