Neurogenetics最新文献

ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential. ZNRF3在神经发育障碍中的作用：对Wnt信号传导和治疗潜力的见解。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-10-02 DOI: 10.1007/s10048-025-00852-5

Yasmin Yusuf Hussein Dinle, Ruping Liu, Mainak Sengupta, Rakesh Kumar Panjaliya, Parimal Das, Anjana Munshi, Samraggi Chakraborty, Jinghua Li, Baiyu Qi, Zakaria Ahmed Mohamed, Qian Tong, Mingyou Zhang, Jianping Wen, Santasree Banerjee

{"title":"ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential.","authors":"Yasmin Yusuf Hussein Dinle, Ruping Liu, Mainak Sengupta, Rakesh Kumar Panjaliya, Parimal Das, Anjana Munshi, Samraggi Chakraborty, Jinghua Li, Baiyu Qi, Zakaria Ahmed Mohamed, Qian Tong, Mingyou Zhang, Jianping Wen, Santasree Banerjee","doi":"10.1007/s10048-025-00852-5","DOIUrl":"https://doi.org/10.1007/s10048-025-00852-5","url":null,"abstract":"Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and intellectual disabilities (ID), have seen an increasing prevalence in recent years. Both genetic and environmental factors have been implicated in the pathogenesis of these conditions. One such gene, ZNRF3, plays a pivotal role in regulating neural cell growth and connectivity, with variations in this gene linked to disruptions in neural differentiation and communication. This review synthesizes genetic, molecular, and clinical research to examine the role of ZNRF3 in brain development. Furthermore, it explores the impact of prenatal environmental exposures and healthcare policies on diagnostic practices and treatment accessibility. The findings highlight the need for improved genetic screening, early intervention strategies, and policy reforms aimed at facilitating personalized care for individuals affected by ZNRF3-related NDDs.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"72"},"PeriodicalIF":1.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the ethnic and clinical spectrum of the IDS c.1122C>T mutation: first report from Pakistan. 扩大IDS c.1122C >t突变的种族和临床谱：来自巴基斯坦的第一份报告

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-10-01 DOI: 10.1007/s10048-025-00845-4

Sana Fatima, Hunza Malik, Aftab Ali, Nisar Ahmad, Maria Shafiq, Muhammad Abdullah, Jabbar Khan, Hadia Gul, Muzammil Ahmad Khan, Muhammad Muzammal

{"title":"Expanding the ethnic and clinical spectrum of the IDS c.1122C>T mutation: first report from Pakistan.","authors":"Sana Fatima, Hunza Malik, Aftab Ali, Nisar Ahmad, Maria Shafiq, Muhammad Abdullah, Jabbar Khan, Hadia Gul, Muzammil Ahmad Khan, Muhammad Muzammal","doi":"10.1007/s10048-025-00845-4","DOIUrl":"https://doi.org/10.1007/s10048-025-00845-4","url":null,"abstract":"Hunter syndrome, also known as Mucopolysaccharidosis type II (MPS II), is a rare X-linked lysosomal storage disorder caused by mutations in the IDS, which encodes the iduronate-2-sulfatase enzyme. The main aim of the current genetic study was to investigate a non-consanguineous Pakistani family segregating Hunter's syndrome. Clinical evaluation, biochemical assays, radiological imaging, and genetic sequencing were performed on the affected individuals. The Family was recruited from Khyber Pakhtunkhwa (KP) province of Pakistan and has two affected male individuals. Routine blood investigations showed low blood sugar (1/2), elevated SGPT (1/2), and increased RDW-CV levels (2/2). Both patients (2/2) presented with a severe phenotype, including cognitive impairment (2/2), coarse facial features (2/2), skeletal abnormalities (2/2), growth delay (2/2), hepatomegaly (2/2), hydrocephalus (2/2), macrocephaly (2/2), visual impairment (2/2), and restricted joint mobility (2/2). A previously reported hemizygous c.1122C>T mutation in exon 8 of the IDS. The identified mutation presumably creates an aberrant splicing and leads to the deletion of 20 amino acids in the open reading frame, which would distort the local folding of the polypeptide chain and lead to loss of its interacting sites. MRI analysis demonstrated typical MPS-II-related abnormalities, including enlarged perivascular spaces, ventriculomegaly, posterior fossa and sella turcica deformities, and spinal cord compression due to periodontoid thickening and spinal stenosis. Although the c.1122C>T (IDS) mutation is not novel, its identification in a Pakistani Pashtun family is reported here for the first time, contributing to the ethnic and geographic mapping of MPS II. This study underscores the importance of population-specific mutation data for effective genetic counseling, early diagnosis, and carrier screening.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"71"},"PeriodicalIF":1.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternative splicing events of three rare variants in CHKB gene causing megaconial congenital dystrophy. CHKB基因三种罕见变异引起巨头先天性营养不良的选择性剪接事件。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-09-30 DOI: 10.1007/s10048-025-00851-6

Francisco Javier Cotrina-Vinagre, María Elena Rodríguez-García, María Martín-Cazaña, Agustín Cárdenas Del Carre, Montserrat Morales-Conejo, Elena Martín-Hernández, Francisco Martínez-Azorín

{"title":"Alternative splicing events of three rare variants in CHKB gene causing megaconial congenital dystrophy.","authors":"Francisco Javier Cotrina-Vinagre, María Elena Rodríguez-García, María Martín-Cazaña, Agustín Cárdenas Del Carre, Montserrat Morales-Conejo, Elena Martín-Hernández, Francisco Martínez-Azorín","doi":"10.1007/s10048-025-00851-6","DOIUrl":"https://doi.org/10.1007/s10048-025-00851-6","url":null,"abstract":"We report the case of a Spanish female patient with progressive myopathy and severe muscle atrophy, intellectual delay, absence of expressive language development, overweight, and mitochondrial abnormalities. Whole-exome sequencing uncovered three heterozygous CHKB variants in the patient, one from the paternal allele and two from de maternal allele (NC_000022.11(NM_005198.5): c. [581G > A];[843 T > C;1031 + 3G > C]). This gene encodes the Choline/ethanolamine kinase (CHKB) protein, which catalyzes the first step of phosphatidylcholine biosynthesis. Pathogenic CHKB variants have been associated with megaconial congenital muscular dystrophy (MDCMC). In order to assess the pathogenicity of these variants, expression experiments of RNA for CHKB were carried out by RT-PCR from lymphocytes. The c.581G > A variant, instead to produce a missense change (p.Arg194Gln), induces an aberrant splicing event resulting in the deletion of exon 4 (V1 and V2: r.448_581del). On the other hand, the other two variants (c.843 T > C (p.Phe281 =) and c.1031 + 3G > C splice site variant) induces five alternative splicing events by altering the splice sites of exons 8 and 9 (V3: r.928_1031del, V4: r.970_1033del, V5: r.1026_1033del, V6: r.820_1032del and V7: r.819_927del). In all cases, the predicted codified proteins are truncated in carboxy-terminus, affecting to important domains of the protein or are likely to be degraded by NMD. In conclusion, we describe for the first time the pathological mechanism of the c.581G > A variant, show that c.843 T > C (synonymous variant) might be responsible for the exon 8 skipping, and confirm that c.1031 + 3G > C induces differential splicing as previously shown. Consequently, our findings provide additional functional evidences associated with CHKB variants.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"70"},"PeriodicalIF":1.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into the heterogeneity of oculopharyngeal muscular dystrophy. 对眼咽肌营养不良异质性的认识。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-09-24 DOI: 10.1007/s10048-025-00849-0

Kyriaki Kekou, Constantinos Papadopoulos, Maria Svingou, Margarita Chrysanthou-Piterou, Evangelia Nitsa, Danai Veltra, Nikos Marinakis, Faidon-Nikolaos Tilemis, Parissis Dimitrios, Marianthi Arnaoutoglou, Maria Moschou, Sophia Xirou, Christos Bakirtzis, Georgios Tsivgoulis, Giorgos-Konstantinos Papadimas, Christalena Sofocleous

{"title":"Insights into the heterogeneity of oculopharyngeal muscular dystrophy.","authors":"Kyriaki Kekou, Constantinos Papadopoulos, Maria Svingou, Margarita Chrysanthou-Piterou, Evangelia Nitsa, Danai Veltra, Nikos Marinakis, Faidon-Nikolaos Tilemis, Parissis Dimitrios, Marianthi Arnaoutoglou, Maria Moschou, Sophia Xirou, Christos Bakirtzis, Georgios Tsivgoulis, Giorgos-Konstantinos Papadimas, Christalena Sofocleous","doi":"10.1007/s10048-025-00849-0","DOIUrl":"10.1007/s10048-025-00849-0","url":null,"abstract":"Oculopharyngeal muscular dystrophy (OPMD) is a rare, adult-onset, autosomal dominant myopathy characterized by variability in the age of onset and disease progression. However, its pathogenesis and phenotypic variability remain poorly understood. The disorder is caused by an expansion of a short polyalanine tract in the poly(A) binding protein nuclear 1 (PABPN1) gene. This study presents data from 23 patients across 19 Greek families with pathogenic PABPN1 expansions, including demographic and laboratory data, as well as molecular and electron microscopy findings. Eight distinct trinucleotide expansion genotypes were identified. Electron microscopy consistently demonstrated mitochondrial abnormalities, including swelling, disrupted cristae and atypical lipid inclusions. Clinical heterogeneity was observed at both inter- and intrafamilial levels, and milder phenotypes were generally linked to smaller alleles. Notably, maternally inherited expansions were associated with an earlier disease onset and more severe progression in affected offspring. Given the genetic variability observed in the cohort, the presence of a founder effect could not be supported. A significant degree of underdiagnosis or diagnostic delay was noted, largely attributable to the rarity and clinical heterogeneity of the disease. The observed intrafamilial heterogeneity - particularly in maternally inherited expansions - supports previous reports suggesting that mitochondrial dysfunction may contribute to transgenerational disease progression in the context of a dominant, causative nuclear variant.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"68"},"PeriodicalIF":1.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel hybrid deep learning model for segmentation and uzzy Res-LeNet based classification for Alzheimer's disease. 基于模糊Res-LeNet的阿尔茨海默病分割和分类混合深度学习模型。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-09-24 DOI: 10.1007/s10048-025-00837-4

Soujanya R, Syamala Maganti, Sai Hanuman Akundi

{"title":"A novel hybrid deep learning model for segmentation and uzzy Res-LeNet based classification for Alzheimer's disease.","authors":"Soujanya R, Syamala Maganti, Sai Hanuman Akundi","doi":"10.1007/s10048-025-00837-4","DOIUrl":"10.1007/s10048-025-00837-4","url":null,"abstract":"Alzheimer's disease (AD) is a progressive illness that can cause behavioural abnormalities, personality changes, and memory loss. Early detection helps with future planning for both the affected person and caregivers. Thus, an innovative hybrid Deep Learning (DL) method is introduced for the segmentation and classification of AD. The classification is performed by a Fuzzy Res-LeNet model. At first, an input Magnetic Resonance Imaging (MRI) image is attained from the database. Image preprocessing is then performed by a Bilateral Filter (BF) to enhance the quality of image by denoising. Then segmentation is carried out by the proposed O-SegUNet. This method integrates the O-SegNet and U-Net model using Pearson correlation coefficient-based fusion. After the segmentation, augmentation is carried out by utilizing Synthetic Minority Oversampling Technique (SMOTE) to address class imbalance. After that, feature extraction is carried out. Finally, AD classification is performed by the Fuzzy Res-LeNet. The stages are classified as Mild Cognitive Impairment (MCI), AD, Cognitive Normal (CN), Early Mild Cognitive Impairment (EMCI), and Late Mild Cognitive Impairment (LMCI). Here, Fuzzy Res-LeNet is devised by integrating Fuzzy logic, ResNeXt, and LeNet. Furthermore, the proposed Fuzzy Res-LeNet obtained the maximum performance with an accuracy of 93.887%, sensitivity of 94.587%, and specificity of 94.008%.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"69"},"PeriodicalIF":1.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bridging the gap: pyridoxine-dependent epilepsy (PDE-ALDH7A1) diagnosis and management in a low-resource setting. 弥合差距：在低资源环境中吡哆醇依赖性癫痫（PDE-ALDH7A1）的诊断和管理。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-09-19 DOI: 10.1007/s10048-025-00850-7

Andika Priamas Nugrahanto, Agung Triono, Neti Nurani, Kristy Iskandar, Dian Kesumapramudya Nurputra, Irma Sri Hidayati, Elisabeth Siti Herini

引用次数: 0

Huntington's chorea: emerging fields in therapeutics (Review). 亨廷顿舞蹈病：治疗学的新兴领域（综述）。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-09-06 DOI: 10.1007/s10048-025-00848-1

Aisha Tahir, Sania Jamal, Usman Ali Shams, Saqib Mehmood

引用次数: 0

Familial cerebral cavernous malformations caused by a novel germline structural variant in the KRIT1 gene. KRIT1基因的一种新的种系结构变异引起的家族性脑海绵状血管瘤。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-08-28 DOI: 10.1007/s10048-025-00847-2

Robin A Pilz, Matthias Begemann, Surema Pfister, Paranchai Boonsawat, Anita Rauch, Ingo Kurth, Ute Felbor, Matthias Rath

引用次数: 0

Schinzel-Giedion syndrome: communication, feeding and motor skills in 16 individuals. Schinzel-Giedion综合征：16个个体的沟通、喂养和运动技能。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-08-27 DOI: 10.1007/s10048-025-00846-3

Lottie D Morison, Nuala Summerfield, Dana Bradley, Bregje W van Bon, Angela T Morgan

{"title":"Schinzel-Giedion syndrome: communication, feeding and motor skills in 16 individuals.","authors":"Lottie D Morison, Nuala Summerfield, Dana Bradley, Bregje W van Bon, Angela T Morgan","doi":"10.1007/s10048-025-00846-3","DOIUrl":"10.1007/s10048-025-00846-3","url":null,"abstract":"Schinzel-Giedion Syndrome (SGS) is a rare neurodevelopmental disorder caused by pathogenic SETBP1 gain-of-function variants. SGS medical features have been well described. Associated skills critical to quality of life have such as communication, feeding, and motor skills are yet to be characterised. Here we used standardised caregiver report tools to characterise these skills as well as the medical features, in 16 children with SGS (median = 5 years, 7 months, range 6 months to 12.5 years). Vineland-3 scores reflected severe impairment in communication, daily living, socialisation and motor skills. Average receptive and expressive language skills were equivalent to a 0-to-1-month-old. Average motor skills were slightly stronger with age equivalents of 2-months-old for gross motor skills and 4-months for fine motor skills. 13/16 (81%) children could attend to someone's voice, and 15/16 (94%) could make happy vocalisations. One individual (6%) could follow basic instructions. Despite a relatively homogenous phenotype, some children presented with relative strengths when compared to the rest of the cohort. Our expanded phenotype of SGS allows better targeted therapies and supports, highlighting the importance of early feeding intervention and augmentative and alternative communication (e.g., assistive technology for communication). Given the severity of the SGS profile, our data highlight the need for sensitive measurement tools for detecting subtle skill changes in SGS in response to precision medicine interventions.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"64"},"PeriodicalIF":1.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathogenic KCNH2 variant in monozygotic twins with speech delay and lower risk type 2 long QT syndrome. 致病性KCNH2变异在言语迟缓和低风险2型长QT综合征的同卵双胞胎中。

IF 1.2 4区医学

Neurogenetics Pub Date : 2025-08-15 DOI: 10.1007/s10048-025-00842-7

Katia Margiotti, Marco Fabiani, Costanza Zangheri, Antonella Cima, Francesca Monaco, Francesco Libotte, Chiara Ali', Maria Antonietta Barone, Antonella Viola, Alvaro Mesoraca, Claudio Giorlandino

{"title":"Pathogenic KCNH2 variant in monozygotic twins with speech delay and lower risk type 2 long QT syndrome.","authors":"Katia Margiotti, Marco Fabiani, Costanza Zangheri, Antonella Cima, Francesca Monaco, Francesco Libotte, Chiara Ali', Maria Antonietta Barone, Antonella Viola, Alvaro Mesoraca, Claudio Giorlandino","doi":"10.1007/s10048-025-00842-7","DOIUrl":"10.1007/s10048-025-00842-7","url":null,"abstract":"Type 2 Long QT Syndrome (type 2 LQTS) is a cardiac channelopathy caused by pathogenic variants in the KCNH2 gene, often associated with delayed cardiac repolarization and increased risk of arrhythmias. While its impact is traditionally considered cardiac, emerging studies suggest a potential role of KCNH2 dysfunction in neurogical disorders. We describe monozygotic twin sisters carrying the pathogenic frameshift variant KCNH2 c.2959_2960delCT (p.Leu987Valfs*131; rs748706373), inherited from their asymptomatic father. Clinically, both twins presented with severe language delay, absence of pointing, impaired social interaction, and stereotyped behaviors features consistent with neurogical disorders. Diagnostic diagnostic testing included whole exome sequencing (WES), chromosomal microarray (aCGH), and Fragile X screening. The KCNH2 variant emerged as the sole clinically significant finding. Cardiac evaluation through ECG and 24-hour Holter monitoring revealed no significant QT prolongation or arrhythmic episodes in either the twins or their father. No history of syncope, seizures, or cardiac events was reported. This report supports the variable expressivity and incomplete penetrance of KCNH2 variants in type 2 LQTS and raises the possibility that KCNH2 dysfunction may contribute to neurogical phenotypes manifestations. Causality remains to be established between KCNH2 and neurologic disorders. Though whole-genome sequencing remains to be completed in this pedigree, the potential association between KCNH2 and neurologic disorders is strengthened by the unique monozygotic presentation and the absence of known perinatal complications. Further studies are needed to clarify the association between KCNH2 variants and their contribution to neurological disorders, either through direct neural effects or indirectly via unrecognized perinatal arrhythmic events.","PeriodicalId":56106,"journal":{"name":"Neurogenetics","volume":"26 1","pages":"63"},"PeriodicalIF":1.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0