Molecular Genetics & Genomic Medicine最新文献

{"title":"A Retrospective Study of Infant and Maternal Risk Factors in LUMBAR Syndrome.","authors":"Denise W Metry, Dawn H Siegel, Kim M Keppler-Noreuil","doi":"10.1002/mgg3.70093","DOIUrl":"10.1002/mgg3.70093","url":null,"abstract":"<p><strong>Background: </strong>LUMBAR syndrome is the association of segmental infantile hemangiomas that affect the Lower part of the body with Urogenital anomalies, hemangioma Ulceration, spinal cord Malformations, Bony deformities, Anorectal malformations, Arterial anomalies and/or Renal anomalies. The etiology is not known but is suspected to be multifactorial, involving genetic and environmental factors.</p><p><strong>Methods: </strong>We retrospectively reviewed a large database of 109 published reports of LUMBAR syndrome to study potential associated clinical risk factors, the first such effort.</p><p><strong>Results: </strong>LUMBAR is significantly more common in full-term, normal birth weight, singleton girls. We found no statistically significant differences in disease severity between affected girls and boys. There were no reports in twins or other multiple births, no reports of familial recurrence, and no repeated maternal illnesses, exposures, or other prenatal risk factors.</p><p><strong>Conclusions: </strong>Prospective studies in LUMBAR syndrome are needed to further evaluate maternal risk factors for prenatal hypoxia, gene-environment interactions, and genetic susceptibility variants.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 4","pages":"e70093"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795946","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}

{"title":"A Novel YWHAG Variant L173S Causes Developmental and Epileptic Encephalopathy by Disrupting the Hydrophobic Internal Protein Structure.","authors":"Yuan Jin, Qian Niu, Shan Na Liang, Mei Ling Luo, Xiao Lin Su, Zhe Tao","doi":"10.1002/mgg3.70079","DOIUrl":"10.1002/mgg3.70079","url":null,"abstract":"<p><strong>Background: </strong>Developmental epileptic encephalopathy 56 (DEE56) is a monogenic DEE type caused by heterozygous mutations in YWHAG. To our knowledge, fewer than 30 cases of DEE56 have been reported globally, and our understanding of YWHAG's function remains limited.</p><p><strong>Methods: </strong>Whole exome sequencing (WES) was performed on the patient and his parents. Structural conservation analysis of YWHAG was conducted using Consurf and PyMol. A literature search for relevant cases was performed in PubMed and Google Scholar.</p><p><strong>Results: </strong>The patient is a 6-year-2-month-old boy who developed refractory complex seizures starting at 8 months of age. He also exhibits intellectual disability, language impairment, and poor motor coordination. WES identified the de novo occurrence of a novel heterozygous YWHAG missense variant, c.518T>C (p.L173S), in the patient. L173 resides within the hydrophobic internal core formed by three alpha helices of YWHAG, and the residues constituting this internal core are highly evolutionarily conserved. The L173S substitution introduces a hydrophilic side chain into the hydrophobic core composed of three aliphatic residues. Ten missense mutations have been reported previously. Among them, five (E15, R57, D129, R132, and Y133) are associated with the ligand-binding region.</p><p><strong>Conclusion: </strong>The functional domain involving the L173 residue of YWHAG remains unknown. Our findings suggest that the disruption of the stability of the highly conserved internal core of the YWHAG protein may be one mechanism leading to functional impairment, distinct from the previously proposed pathogenic models of dimer formation defects and/or impaired binding to phosphopeptide ligands. This may provide insights into the functional mechanisms of YWHAG and potential therapeutic strategies.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 4","pages":"e70079"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729919","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}

{"title":"Expanding the Clinical and Genetic Spectrum of Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency: Insights From Two Unrelated Chinese Families.","authors":"Jihua Wu, Xuehui Hu, Zhongli Zhao, Zhen Zhao, Bin Yang","doi":"10.1002/mgg3.70097","DOIUrl":"10.1002/mgg3.70097","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) is a rare autosomal recessive disorder affecting valine metabolism, with clinical severity ranging from neonatal death to survival into adulthood. Despite advances in understanding ECHS1D, the genetic basis remains underexplored, particularly in underrepresented populations.</p><p><strong>Methods: </strong>This study aimed to investigate the clinical and genetic characteristics of ECHS1D in two unrelated Chinese families and identify novel pathogenic variants. Clinical and genetic data were collected, and whole-genome sequencing was performed to identify pathogenic variants in the ECHS1 gene.</p><p><strong>Results: </strong>The first proband, a 15-month-old girl, presented with developmental delays and metabolic acidosis, with an MRI revealing abnormal signals in the basal ganglia. The second proband, a 6.5-year-old girl with movement-induced dystonia, exhibited lethargy following recurrent fever and vomiting, with similar MRI findings. Genetic testing identified novel compound heterozygous variants: c.759_762del (p.Gly255Valfs*21) and c.489G>A (p.Pro163=) in Proband 1 and c.518C>T (p.Ala173Val) and c.244G>A (p.Val82Met) in Proband 2. The c.759_762del (p.Gly255Valfs21) variant, identified for the first time, likely results in severe symptoms due to a loss of normal function.</p><p><strong>Conclusion: </strong>These findings expand the ECHS1 mutational spectrum and emphasize the importance of genetic testing for early diagnosis and personalized management of ECHS1D. Interventions such as dietary valine restriction and the avoidance of triggering factors may improve clinical outcomes, while further research is needed to explore targeted therapeutic strategies.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 4","pages":"e70097"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11973933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795948","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}

{"title":"Identification of Compound Heterozygous Variants in OBSCN Gene Associated With Rhabdomyolysis: A Case Report.","authors":"Xiaolan Sun, Yong Chen, Jianmin Zhong, Hui Chen, Jihua Xie, Ruiyan Wang","doi":"10.1002/mgg3.70094","DOIUrl":"10.1002/mgg3.70094","url":null,"abstract":"<p><strong>Background: </strong>The obscurin protein encoded by the OBSCN gene is an important structural protein in the regulation of myocyte sarcoplasmic nodule stability and sarcoplasmic reticulum function and is particularly closely associated with calcium ion (Ca²⁺) signaling. With increasing genomic studies, pathogenic variants in the OBSCN gene have been shown to be associated with a variety of inherited diseases, such as cardiomyopathy. However, case reports of its variants causing rhabdomyolysis are more limited.</p><p><strong>Methods: </strong>We performed whole exome sequencing on a patient with exercise-induced rhabdomyolysis to identify possible causative gene variants. In addition, functional prediction of the pathogenicity of the variants was performed by combining multiple bioinformatics analysis tools and in-depth analyses with clinical phenotypes and family history.</p><p><strong>Results: </strong>The patient carried compound heterozygous variants, including c.21184C>T (nonsense variant) and c.15610+12C>T (intronic splicing variant). The c.21184C>T variant resulted in a premature termination of the protein, was not included in population-based databases, and was supported by multiple prediction tools as a potentially pathogenic variant. The c.15610+12C>T variant was also absent in the gnomAD_EAS database and predicted to disturb normal splicing, potentially creating a novel donor site. The pathogenicity of the variant is further supported by the fact that the patient's mother, with a homozygous OBSCN variant, also exhibited exercise-induced myalgia. Clinically, the patient presented with exercise-induced rhabdomyolysis accompanied by significant serum creatine kinase elevation, muscle pain, and MRI-demonstrated muscle edema of both lower limbs without significant muscle weakness or cardiac abnormalities.</p><p><strong>Conclusion: </strong>We report the first case of rhabdomyolysis in China caused by OBSCN gene variants. This finding further extends the spectrum of the OBSCN gene variants. It also provides an important basis for genetic counseling and helps in the early diagnosis and management of similar cases.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 4","pages":"e70094"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788605","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}

{"title":"Novel Compound Heterozygous Variants in ZNF526 Causing Dentici-Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review.","authors":"Shaoxin Li, Hui Fang, Hong Li, Min Peng, Jinsong Bao, Yunfei Cai, Jing Chen, Zhige Li","doi":"10.1002/mgg3.70089","DOIUrl":"10.1002/mgg3.70089","url":null,"abstract":"<p><strong>Background: </strong>The ZNF526 gene encodes a ubiquitously expressed Kruppel-type zinc finger protein crucial in transcriptional regulation. Recent studies suggest that biallelic pathogenic variants in ZNF526 may lead to Dentici-Novelli neurodevelopmental syndrome, characterized by microcephaly, developmental delay, epilepsy, and ocular anomalies. To date, phenotypic details have been reported for only six patients with ZNF526 variants.</p><p><strong>Methods: </strong>This study gathered clinical information and genetic data from a child with neurodevelopmental disorders. A three-dimensional protein model was employed to predict variant effects on protein structure. A literature review was conducted to compare this case with previously reported cases, analyzing clinical features and genetic findings.</p><p><strong>Results: </strong>The proband, a 7-month-old girl, exhibited developmental delay, microcephaly, limb hypotonia, abnormal brain imaging, and seizures. Chromosomal karyotype analysis and copy number variation analyses were normal. Whole exome sequencing revealed two heterozygous variants in the ZNF526 gene (NM_133444.3): c.1426del (p.Val476Phefs*9), a de novo frameshift variant, and c.1513T;> C (p.Cys505Arg), inherited from her mother. These previously unreported variants are on separate alleles, forming a compound heterozygous state correlated with the clinical presentation. Ocular anomalies were absent, while café-au-lait spots may represent a novel feature. Among 12 cases of Dentici-Novelli neurodevelopmental syndrome, 11 unique ZNF526 variants have been identified, with loss-of-function variants possibly linked to seizures.</p><p><strong>Conclusion: </strong>This study describes the youngest patient with Dentici-Novelli neurodevelopmental syndrome, broadening the ZNF526 mutation spectrum and detailing the associated clinical profile. These findings are valuable for genetic diagnosis and family counseling in cases of this syndrome.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 4","pages":"e70089"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803834","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}

{"title":"Reporting a Homozygous Case of Neurodevelopmental Disorder Associated With a Novel PRPF8 Variant.","authors":"Mohammad Reza Mirinezhad, Farzaneh Mirzaei, Arash Salmaninejad, Reza Jafarzadeh Esfehani, Mohammad Reza Seyedtaghia, Sheyda Farahmand, Mehran Beiraghi Toosi, Somayyeh Hashemian, M E Suzzane Lewis","doi":"10.1002/mgg3.70084","DOIUrl":"10.1002/mgg3.70084","url":null,"abstract":"<p><strong>Background: </strong>While recently identified heterozygous PRPF8 variants have been linked to various human diseases, their role in neurodevelopmental disorders (NDDs) remains ambiguous. This study investigates the potential association between homozygous PRPF8 variants and NDDs. Most PRPF8 variants are primarily associated with retinal diseases; however, we analyze a family with multiple members diagnosed with NDDs.</p><p><strong>Methods: </strong>Using exome sequencing (ES), the cause of behavioral problems and intellectual disabilities (IDs) of two sisters from a consanguineous parents was solved, and the results confirmed by direct sanger sequencing method likewise protein modeling to assess the structural impact of the identified variant on the PRPF8 protein has been done.</p><p><strong>Results: </strong>ES identified a novel homozygous variant, PRPF8 c.257G>T, p.R86M. To the best of our knowledge at the time of writing this manuscript, the mentioned variant has not been reported in relation to NDDs. Protein modeling provided another line of evidence proving the pathogenicity of the novel variant.</p><p><strong>Conclusion: </strong>Our findings indicate that the p.R86M variant may disrupt normal protein function by changing its structure and probably its interaction, potentially leading to the observed neurodevelopmental phenotypes. This study highlights the first link between the PRPF8 variant and NDDs, suggesting a distinct role for specific PRPF8 variants in the etiology of NDDs. These results warrant further investigation into the mechanisms by which PRPF8 variants contribute to NDDs, emphasizing the need for comprehensive genetic screening in families with unexplained neurodevelopmental conditions.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70084"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597307","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}

{"title":"Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation.","authors":"Mathis Lepage, Nancy Uhrhammer, Ioana Molnar, Maud Privat, Flora Ponelle-Chachuat, Mathilde Gay-Bellile, Yannick Bidet, Mathias Cavaillé","doi":"10.1002/mgg3.70086","DOIUrl":"10.1002/mgg3.70086","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple primary malignancies (MPMs) refer to two or more primary malignant tumors in the same patient. MPMs are frequent: 18.4% of incident cancers represent a second or a higher primary cancer. In order to assess the value of genetic testing for patients with multiple cancers, studies are needed to accurately determine the prevalence of pathogenic variants for these patients.</p><p><strong>Methods: </strong>All families were seen in our oncogenetics consultation from 2010 to 2022. We compared clinical features and detection rates of pathogenic or likely pathogenic variants in a panel of up to 47 cancer predisposition genes in patients with ≥ 2 primary cancers (n = 348) versus a single primary cancer (n = 1422).</p><p><strong>Results: </strong>A pathogenic or likely pathogenic variant was diagnosed in 27.3% of patients with 348 index patients with MPM, concerning 21 genes: BRCA1 (n = 27), BRCA2 (n = 19), MSH2 (n = 9), ATM (n = 8), MLH1 (n = 5), MSH6 (n = 6), TP53 (n = 4), CHEK2 (n = 4), PALB2 (n = 3), APC (n = 2), MEN1 (n = 1), RAD51C (n = 1), NBN (n = 1), EPCAM (n = 1), PMS2 (n = 1), RB1 (n = 1), PTEN (n = 1), CYLD1 (n = 1), NF1 (n = 1), RAD51D (n = 1), and CDKN2A (n = 1). MPM index cases were more likely to carry a deleterious mutation than cases with a single cancer (27.3% vs. 11.39%, p < 0.001). Pathogenic variants were found more frequently in patients with a suggestive family history (34.2% vs. 20.1%, p < 0.05), with a younger age of cancer diagnosis related to the suspected syndrome (32.7% vs. 22%, p = 0.049). For the 208 index patients with ≥ 2 cancers pertaining to the same predisposition syndrome (HBOC, HNPCC…), the detection rate increased significantly to 36% (vs. 14.3% for MPM patients with unrelated cancers (n = 140), p < 0.001). Conversely, the detection rate for patients with unrelated cancers was not statistically different from the single-cancer population (14.3%-11.39%, p = 0.318).</p><p><strong>Conclusion: </strong>Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70086"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531649","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}

{"title":"A KCNQ4 Gene Variant (c.701A > G; p.His234Arg) in a Chinese Family With Nonsyndromic Deafness 2A.","authors":"Guo-Qing Gong, Cheng-Cheng Huang, Hui-Yu Jin, Zhao Zhang, Chang-Liang Yang, Guang Yang, Hui-Fang Lu, Yue-Bin Yang, Jing-Yuan Cao, Rui-Yao Chen, Li-Wang, Yi-Ming Ji, Yi Sun, Yu Lu","doi":"10.1002/mgg3.70075","DOIUrl":"10.1002/mgg3.70075","url":null,"abstract":"<p><strong>Background: </strong>KCNQ4 is a common genetic cause of nonsyndromic autosomal dominant hearing loss. We have identified the family in China with a KCNQ4 (c.701A>G; p.His234Arg) missense variation. In this study, a survey and analysis were performed to investigate the audiological and genetic characteristics of the Chinese family.</p><p><strong>Methods: </strong>The medical history of family members was collected, and the family members underwent pure tone audiometry, acoustic immittance, and physical examination. The proband was additionally examined by ABR (auditory brainstem response) and DPOAE (distortion product otoacoustic emission). DNA samples from family members were collected, and the possible causative gene of the proband was detected by whole-exome sequencing (WES), which was verified by Sanger sequencing in family members.</p><p><strong>Results: </strong>The inheritance pattern of the family was an autosomal dominant nonsyndromic type. The hearing loss was characterized by postlingual deafness, high-frequency hearing loss in the early stage, gradually involving the full frequency. About 32-40 years of age, the hearing gradually became stable, the decline rate slowed down, and the final degree of hearing loss was severe. WES results showed that the KCNQ4 gene had a missense variation (c.701A>G; p.His234Arg).</p><p><strong>Conclusion: </strong>This family has autosomal dominant nonsyndromic hereditary hearing loss caused by a variation in the KCNQ4 gene, characterized by high-frequency hearing loss.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70075"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573001","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}

{"title":"A Novel Variant in Dentin Sialophosphoprotein (DSPP) Gene Causes Dentinogenesis Imperfecta Type III: Case Report.","authors":"Yan Wang, Ximin Xu, Yuzhe Ding, Guohua Yuan","doi":"10.1002/mgg3.70087","DOIUrl":"10.1002/mgg3.70087","url":null,"abstract":"<p><strong>Background: </strong>Hereditary dentin defects are a group of autosomal dominant disorders characterized by developmental abnormalities in dentin formation and mineralization. They can be categorized into dentin dysplasia and dentinogenesis imperfecta.</p><p><strong>Methods: </strong>In this study, we report a Chinese family with dentinogenesis imperfecta type III (DGI-III). The proband, a 3-year-old girl, and her mother showed extremely rapid attrition and opalescent discoloration in their teeth. Besides, the primary teeth of the proband showed \"shell teeth\" radiographically, a phenotype characterized by abnormally enlarged pulp cavities and thin dentin, which are specific features of DGI-III. The clinical data was collected and the genomic DNA was extracted from their peripheral blood samples. Whole-exome sequencing and Sanger sequencing were performed to screen for variations. Then we preliminarily evaluated the secretion of the dentin sialophosphoprotein (DSPP) variant of this family and compared this variant with wild-type DSPP via western blot (WB) analysis in vitro.</p><p><strong>Results: </strong>The results revealed a novel variant (NM_014208: exon2: c.38C>A: p.A13E) in the signal peptide coding region of the DSPP gene in both the proband and her mother, but not in her father, who had normal teeth. The secretion of the variant DSPP protein was not detected in Human embryonic kidney 293E cells via WB analysis.</p><p><strong>Conclusion: </strong>Taken together, this study describes the clinical features and genetic etiology of a family with DGI-III, expanding the range of variants that cause DGI-III and enriching the phenotypes associated with variants in the signal peptide segment of DSPP. Functional analysis reveals that this variant disrupts DSPP protein secretion.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70087"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557341","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}

{"title":"A Mutation in the ANK2 Gene Causing ASD and a Review of the Literature.","authors":"Lu Zhao, Zhi-Dong Qiao, Yue-Xin Jia, Jun-Xian Fu, Tian-Xia Li, Kai-Ru Jia, Hong Zhao, Jin-Ping Bao, Xiao-Fan Yang, Hao Pan, Guang-Lu Yang","doi":"10.1002/mgg3.70083","DOIUrl":"10.1002/mgg3.70083","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical and genetic characteristics of patients with ANK2(HGNC:493)-associated autism spectrum disorders (ASDs) and epilepsy (EP).</p><p><strong>Methods: </strong>We identified a novel ANK2 variant in a patient with ASD and EP and summarized the clinical and genetic characteristics of ANK2 gene variants in this patient and those in previous reports.</p><p><strong>Results: </strong>A novel nonsense variant, ANK2 (NM_001148.6):c.3007C>T/p.R1003* in exon 27, was identified in one patient. We described the clinical features and molecular genetics of this patient and previously reported patients. This was discovered at a follow-up visit to the pediatric neurology department where genetic testing based on condition identified this rare genetic variant. He mainly presents with language delay, intellectual disability, limited learning, and communication skills, and later develops seizures, combined with common childhood neurological disorders such as hyperactivity, behavioral abnormalities, and even self-injury. The patient cohort included 16 patients with a complex array of neurological disabilities: ASD (9 patients); EP (10 patients); ASD with EP (4 patients); intellectual disability and developmental delay (5 patients); poor language communication (11 patients); language and learning impairment (11 patients); anxiety/agitation mood disorder (6 patients); attention-deficit/hyperactivity disorder (5 patients); cognitive, memory, and adaptability deficits (1 patient); tic disorder (1 patient); electrocardiogram and cardiac damage (1 patient); and abnormal electroencephalography (EEG) (9 patients).</p><p><strong>Conclusion: </strong>For the first time, we identified a novel variant of the ANK2 gene in China, broadening the genetic spectrum of the ANK2 gene. ANK2 gene mutations can cause ASD, EP, ASD with EP, developmental delay and intellectual disability, poor language communication skills, language and learning disorders, anxiety/agitation mood disorder, and attention-deficit/hyperactivity disorder. Clinical ASD, EP, common EP should consider the ANK2 gene mutation.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 3","pages":"e70083"},"PeriodicalIF":1.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542727","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}