European journal of medical genetics最新文献

{"title":"Innovative treatments of pediatric spinal muscular atrophy: The decision-making process in France","authors":"Maelle Biotteau ,&nbsp;Juliette Ropars ,&nbsp;Brigitte Chabrol ,&nbsp;Isabelle Desguerre ,&nbsp;Christine Barnéria ,&nbsp;Claude Cances","doi":"10.1016/j.ejmg.2025.105044","DOIUrl":"10.1016/j.ejmg.2025.105044","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is a devastating early-onset genetic disease characterized by motor neuron degeneration. For several years, an early access program has facilitated the use of three innovative therapies in France. To better define the therapeutic strategy following innovative therapy approval, an online expert committee within the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) evaluates early diagnosed children and treatment-naive SMA cases during pediatric SMA multidisciplinary team meetings (<em>ps</em>MTMs). The decision process leading to molecule choice or palliative care encompasses pretreatment data collection, case presentation during <em>ps</em>MTMs, decision support, collective decision-making, and consensus, including the place assigned to parents. The process of setting up a nationwide online network of experts seems to be an effective, reactive and useful procedure in choosing the appropriate therapeutic option for newly diagnosed SMA children.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105044"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039508","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":"Rare features in Feingold syndrome type 1","authors":"Fanny Ferroul ,&nbsp;Sarah Snanoudj ,&nbsp;Gaëlle Leterme ,&nbsp;Kheira Mezouaghi ,&nbsp;Marie Kieffer-Traversier ,&nbsp;Tristan Celse ,&nbsp;Jessica Dospeux ,&nbsp;Thomas Huby ,&nbsp;Pauline Marzin ,&nbsp;Godelieve Morel ,&nbsp;Frédérique Payet ,&nbsp;Mathilde Remy ,&nbsp;Laetitia Sennsfelder ,&nbsp;Marta Spondenkiewicz ,&nbsp;Bérénice Roy-Doray ,&nbsp;Jeanne Amiel ,&nbsp;Veronique Pingault ,&nbsp;Jean-Luc Alessandri","doi":"10.1016/j.ejmg.2025.105049","DOIUrl":"10.1016/j.ejmg.2025.105049","url":null,"abstract":"<div><div>Feingold syndrome type 1 (FS1) (OMIM 164280) is an autosomal dominant condition due to heterozygous loss of function variants in <em>MYCN</em> gene or to 2p24 deletion encompassing <em>MYCN</em> gene. The core features of FS1 are digital anomalies, microcephaly, facial dysmorphism, short stature, esophageal/duodenal atresia, and mild learning disabilities. Additional features are reported in a minority of patients, such as cardiac and renal anomalies. Sensorineural deafness is reported in 7 % of the patients. Other features can be associated with classical features of FS1 in patients with 2p deletion including <em>MYCN</em> and other genes. Recently, absence of the flexor pollicis longus tendon has been reported as a new skeletal feature in a pedigree segregating a <em>MYCN</em> variant.</div><div>Here, we reported on three patients having FS1 without gastrointestinal atresia and unusual features: laryngeal cleft, congenital deafness, agenesis of the corpus callosum, and radio ulnar-synostosis (RUS). After the extension of the genetic screening, RUS was considered as an independent condition linked to <em>SMAD6</em> variant.</div><div>Diagnosis of FS1 can be challenging when there are unusual features without digestive malformations drawing attention. In this situation, the diagnostic approach may be based on major criteria of FS1: i) brachymesophalangy of the 2nd and 5th fingers, brachydactyly of fingers and toes with or without 2/3 and/or 4/5 toe syndactylies, ii) microcephaly, and iii) radiographs of the feet to look for amesophalangy of toes. Extension of the genetic screening is required to eliminate the possibility of two independent conditions.</div><div>In addition to the previous recommendations, we advocate for a set of recommendations for evaluation of FS1 patients following initial diagnosis: systematic search of deafness, verification of the flexion of the interphalangeal joints of the thumbs, laryngoscopy in case of stridor or swallowing disorders, and finally systematic cerebral MRI.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105049"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174369","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":"French recommendations on multi-gene panel testing in renal cell carcinoma","authors":"Sophie Giraud ,&nbsp;Pascaline Berthet ,&nbsp;Caroline Abadie ,&nbsp;Nadine Andrieu ,&nbsp;Patrick R. Benusiglio ,&nbsp;Valérie Bonadona ,&nbsp;Olivier Caron ,&nbsp;Carole Corsini ,&nbsp;Isabelle Coupier ,&nbsp;Louise Crivelli ,&nbsp;Capucine Delnatte ,&nbsp;Pierre Devulder ,&nbsp;Antoine DE Pauw ,&nbsp;Sophie Dussart ,&nbsp;Anne-Paule Gimenez-Roqueplo ,&nbsp;Sophie Lejeune-Dumoulin ,&nbsp;Jessica Moretta ,&nbsp;Marie Muller ,&nbsp;Julie Tinat ,&nbsp;Stéphane Richard ,&nbsp;Nelly Burnichon","doi":"10.1016/j.ejmg.2025.105062","DOIUrl":"10.1016/j.ejmg.2025.105062","url":null,"abstract":"<div><h3>Introduction</h3><div>Renal cancers are inherited in about 5 % of cases and are associated with several genetic syndromes. Genetic testing is recommended for selected patients suspected of having hereditary syndromes. In the absence of guidelines regarding which genes should be included for carrying out genetic screening of these individuals, discrepancies existed among the next generation sequencing (NGS) multi-gene panels (MGP) used in French laboratories. There was therefore a clear need to standardise practices and offer patients with renal cancer a consensus-based genetic testing in France.</div></div><div><h3>Methods</h3><div>A working group comprising national experts from the French Genetic and Cancer Group Unicancer (GGC) and from the French network on Hereditary PREDIspositions to Renal Cancer (PREDIR) and encompassing medical geneticists, genetic counsellor, molecular biologists and epidemiologists was established. The objective was to define a list of clinically relevant genes that should be included in a “GGC-PREDIR” approved NGS MGP for patients with renal cancer.</div><div>A list of 32 genes of interest was compiled following an exhaustive and critical review of the literature. The inclusion or exclusion of each gene was determined based on available data regarding risk, prevalence and analyses published from large studies of patients.</div></div><div><h3>Results</h3><div>The French group of experts defined a list of 12 genes of clinical and genetic counselling relevance comprising <em>BAP1</em>, <em>FH</em>, <em>FLCN</em>, <em>MET</em>, <em>PTEN</em>, <em>SDHA</em>, <em>SDHB</em>, <em>SDHC</em>, <em>SDHD</em>, <em>TSC1</em>, <em>TSC2</em> and <em>VHL</em> to be included in the national recommended “renal cancer” NGS MGP. For each of these genes, recommendations for renal surveillance are proposed.</div></div><div><h3>Conclusion</h3><div>Unlike hereditary predisposition to breast or colon cancer, hereditary renal cancer predispositions are rare syndromes and risk estimates are lacking for most of them. Prospective studies are needed to improve our knowledge.</div><div>The GGC-PREDIR experts retained 12 genes for inclusion in the NGS MGP for renal cancer patients. However, the panel will be expanded on the basis of regularly updated data from the medical literature.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105062"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568303","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":"Familial hypertrophic cardiomyopathy associated with TBX1 variation","authors":"Jie Zhang ,&nbsp;Yafei Deng ,&nbsp;Yaxin Huang ,&nbsp;Daoheng Hu ,&nbsp;Haiyan Wu ,&nbsp;Tao Lv ,&nbsp;Weng Yang ,&nbsp;Lilan Wan ,&nbsp;Fang Liu ,&nbsp;Jilin Hu","doi":"10.1016/j.ejmg.2025.105054","DOIUrl":"10.1016/j.ejmg.2025.105054","url":null,"abstract":"<div><h3>Background</h3><div>Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease characterized by significant genetic heterogeneity. While the T-box transcription factor 1 (<em>TBX1</em>) gene is known to cause congenital cardiovascular defects, it has not been previously associated with HCM.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing (WES) was performed to identify causative gene mutations in a recently diagnosed Chinese family with HCM. The mutation was confirmed using Sanger sequencing, which was also employed to investigate familial co-segregation. A literature review was conducted to analyze previously reported <em>TBX1</em> mutations and their associated phenotypes.</div></div><div><h3>Results</h3><div>A novel heterozygous frameshift mutation, <em>TBX1</em> (NM_080647.1):c.3_27dup (p.Met10Alafs∗167), was identified in affected family members. Familial co-segregation analysis revealed that this mutation correlated with the HCM phenotype. To date, no previous studies have reported an association between <em>TBX1</em> mutations and HCM, suggesting that this may represent a novel <em>TBX1</em>-related phenotype.</div></div><div><h3>Conclusion</h3><div>This study identifies familial HCM as a new phenotype linked to <em>TBX1</em> gene mutations. These findings expand the mutation and phenotype spectrum of <em>TBX1</em> and emphasize the need for further research to understand the mechanisms by which the c.3_27dup (p.Met10Alafs∗167) mutation leads to HCM.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105054"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353727","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":"Concurrent inheritance of achromatopsia and MMAT syndrome in a pedigree: Genetic and clinical insights","authors":"Maryam Aghasipour ,&nbsp;Sina Zoghi ,&nbsp;Afrooz Feili ,&nbsp;Hossein Jafari Khamirani ,&nbsp;Mehrdad Afarid ,&nbsp;Ehsan Namvar ,&nbsp;Seyed Alireza Dastgheib ,&nbsp;Seyed Mohammad Bagher Tabei ,&nbsp;Maryam Feili ,&nbsp;Mehdi Dianatpour","doi":"10.1016/j.ejmg.2025.105045","DOIUrl":"10.1016/j.ejmg.2025.105045","url":null,"abstract":"<div><h3>Background</h3><div>Achromatopsia is a rare type of retinal dystrophy presenting with decreased visual acuity, pendular nystagmus, photophobia, impaired color discrimination, and central scotoma. In this study, we investigated achromatopsia in a proband and his family.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing identified two novel variants in <em>PDE6H</em> and <em>ADAMTS18</em>. The presence of the variants was confirmed by Sanger sequencing and it was further utilized to determine the zygosity status of other family members. Lastly, the clinical presentations of the patients were thoroughly assessed.</div></div><div><h3>Results</h3><div>We identified two novel variants in two genes among six patients from a pedigree: <em>PDE6H</em> (NM_006205.3):c.35C &gt; G (p.SER12TER) and <em>ADAMTS18</em> (NM_199355.4):c.3139C &gt; T (p.ARG1047TER). The proband and two of his sisters were homozygous for the variant in PDE6H and heterozygous for the other one. The siblings complained of decreased visual acuity, impaired color discrimination, photophobia, and myopia. Ellipsoid zone disruption and pendular nystagmus were also noted in two and three of the patients, respectively. Two affected patients were heterozygous for the variant identified in <em>PDE6H</em> and homozygous for the variant detected in <em>ADAMTS18</em>. These two are the second generation of the family, born to non-consanguineous parents. Both presented with microcornea, myopia, and telecanthus. Punctual atresia and strabismus were also noted.</div></div><div><h3>Conclusion</h3><div>Pathogenic variants in <em>PDE6H</em> and <em>ADAMTS18</em> can cause a broad range of ophthalmic disorders. We suggest that the study of rare congenital genetic diseases in developing countries should be prioritized due to the differences in their environments and the issues care givers are confronted with when trying to face them.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105045"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063779","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":"ARID1A gene variants and fetal hydrocephalus: First evidence of mRNA decay escape","authors":"Yuya Tanaka ,&nbsp;Mamiko Yamada ,&nbsp;Fuyuki Miya ,&nbsp;Toshimitsu Otani ,&nbsp;Yoshifumi Kasuga ,&nbsp;Hisato Suzuki ,&nbsp;Noboru Inagaki ,&nbsp;Susan M. White ,&nbsp;Mamoru Tanaka ,&nbsp;Kenjiro Kosaki","doi":"10.1016/j.ejmg.2025.105048","DOIUrl":"10.1016/j.ejmg.2025.105048","url":null,"abstract":"<div><div>Germline variants in <em>ARID1A</em> have been associated with the so-called BAFopathies, including Coffin-Siris syndrome, which is characterized by hypertrichosis, short fifth finger, thin upper lip, and thick lower lip, is associated with a unique episignature. Hydrocephalus has not been considered part of BAFopathy until recently, when <em>ARID1A</em> variants were implicated in prenatal-onset hydrocephalus. It remains unknown whether <em>ARID1A</em>-associated hydrocephalus is linked to a specific class of variants and whether it exhibits an episignature comparable to that of BAFopathies. We conducted genomic and epigenomic analyses on a fetus diagnosed with severe hydrocephalus on prenatal ultrasound at 19 weeks. After detailed genetic counseling, the pregnancy was terminated at 21 weeks. The delivered fetus exhibited short fifth fingers, thin upper lip, and thick lower lip. Postmortem exome sequencing using umbilical cord blood identified a <em>de novo</em> heterozygous frameshift variant in the last exon of <em>ARID1A</em> (NM_006015.6:c.5259_5262dupGTCT, p.(Ser1755Valfs∗2)). The frameshift variant in the last exon was expected to escape nonsense-mediated mRNA decay (NMD), and we did confirm this through RNA-seq. Concurrent episignature analysis by nanopore sequencing and a support vector machine-based classifier showed that the fetus maps to the BAFopathy group rather than a separate position on the UMAP. Genotype-phenotype correlation analysis of unpublished data from previous reports regarding hydrocephalus and potential NMD escape, with input from the original authors, indicated that the association remains ambiguous. Hence, <em>ARID1A</em>-associated hydrocephalus occurs within the broader clinical and epigenomic spectrum of BAFopathies, but a distinct genetic mechanism caused by NMD escape is unlikely to play a role.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105048"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079864","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":"Chromosome heteromorphisms: Critical literature review finds No convincing evidence of harm","authors":"Kamlesh Madan","doi":"10.1016/j.ejmg.2025.105056","DOIUrl":"10.1016/j.ejmg.2025.105056","url":null,"abstract":"<div><div>There are conflicting reports on chromosome heteromorphisms. A large number of papers claim that these variants are found more frequently among infertile couples, especially with recurrent pregnancy loss and are even associated with congenital abnormalities. Other studies have found no evidence to support such claims. A critical review of these papers shows that at present there is no convincing evidence to show that heteromorphic chromosome variants, as described in the International System for Human Cytogenomic Nomenclature (ISCN, 2024), are harmful.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105056"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400252","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":"Re-evaluating acceptable risk of death from gene therapy: A threshold study among individuals with Duchenne muscular dystrophy and their caregivers in the US and UK","authors":"Holly Peay ,&nbsp;Ryan Fischer ,&nbsp;Megan McNiff ,&nbsp;Emma Heslop ,&nbsp;Anna Pierce ,&nbsp;Brian Denger ,&nbsp;Eric Camino ,&nbsp;Alexandra Johnson ,&nbsp;Heidi Cope ,&nbsp;Christine Hill ,&nbsp;Katherine L. Beaverson ,&nbsp;Annie Ganot ,&nbsp;Dawn Phillips ,&nbsp;Ione O.C. Woollacott ,&nbsp;Alison Bateman-House ,&nbsp;Kevin M. Flanigan ,&nbsp;Nathalie Goemans ,&nbsp;Laurent Servais ,&nbsp;Michela Guglieri ,&nbsp;Carol Mansfield","doi":"10.1016/j.ejmg.2025.105050","DOIUrl":"10.1016/j.ejmg.2025.105050","url":null,"abstract":"<div><div>Patient and caregiver treatment preferences should be incorporated into the drug development process. We updated a 2018 survey to reflect current knowledge about gene therapy for Duchenne muscular dystrophy (DMD) and obtained new data in the U.S., U.K., and other countries. At data collection in 2023, there were no approved gene therapies for DMD. Using the threshold technique, we assessed the maximum acceptable risk of death (MAR) from non-curative gene therapy with time-limited benefit at different stages of DMD progression. Among 263 participants, mean MAR ranged from 2.4 % (treatment in newborns) to 5.4 % (last year able to lift hands to mouth); risk tolerance increased with advancing disease stages. Significant proportions (22.4 %–32.8 %) were willing to accept MAR &gt;10 %. Reasons for higher MAR included the progressive and severe disease, limited treatment alternatives, and participant-reported expected therapy benefits. Those who demonstrated less risk tolerance described uncertainty, maintaining quality of life, optimism regarding future therapies, and the currently uncertain duration of benefit. There were no significant differences in MAR between caregivers and adults with DMD and between respondents in the U.S. and U.K except in the newborn period, though our small sample size is a limitation. MARs remained relatively stable from 2018 to 2023.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105050"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274179","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":"Diagnostic yield of whole exome sequencing in a cohort of 825 patients","authors":"Peter Førster Andersen ,&nbsp;Jakob Ek ,&nbsp;Helena Gásdal Karstensen ,&nbsp;Mads Bak ,&nbsp;Sabine Weller Grønborg ,&nbsp;Hanne Buciek Hove ,&nbsp;Birgitte Diness ,&nbsp;Tina Duelund Hjortshøj ,&nbsp;Trine Bjørg Hammer ,&nbsp;Christina Høi-Hansen ,&nbsp;Bitten Schönewolf-Greulich ,&nbsp;Anne-Marie Bisgaard ,&nbsp;Morten Duno ,&nbsp;Elsebet Østergaard","doi":"10.1016/j.ejmg.2025.105043","DOIUrl":"10.1016/j.ejmg.2025.105043","url":null,"abstract":"<div><div>Genetic testing plays a significant role in rare disease diagnostics. The most widespread technology for genetic testing of patients is <em>next generation sequencing</em> or <em>second-generation sequencing, including whole exome sequencing</em> (WES). Our laboratory performed diagnostic WES on 1660 samples representing 825 index patients aged 0–84 years between 2014 and 2020. The cohort is comprised of consecutive patients with a rare disease referred for diagnostic WES with analysis of all known disease genes. The main referrals were paediatric, clinical genetic and adult neurology departments.</div><div>Patients’ symptoms were translated to terms in the Human Phenotype Ontology (HPO) system and each symptom assigned to a single top-level HPO term. Variants were classified according to ACMG-AMP guidelines.</div><div>The diagnostic yield in this cohort was 33.7 % with 278 patients receiving a genetic diagnosis.</div><div>Patients with complex phenotypes with involvement of several organ systems were more likely to receive a genetic diagnosis. Higher diagnostic yields were seen for phenotypes including growth abnormalities, abnormalities of the ear or of the musculoskeletal system as well.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105043"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999917","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":"Expansion of the phenotype in ZFX neurodevelopmental disorder in a family","authors":"Linda van der Tol ,&nbsp;Miranda de Jong ,&nbsp;Mariëlle Alders ,&nbsp;Martina Wilke ,&nbsp;Vyne van der Schoot ,&nbsp;Marjon A. van Slegtenhorst ,&nbsp;Anne Goverde","doi":"10.1016/j.ejmg.2025.105053","DOIUrl":"10.1016/j.ejmg.2025.105053","url":null,"abstract":"<div><div>With new and increasingly sensitive techniques for genetic testing, genes that are newly related to a phenotype or disease are still identified, warranting for adequate phenotyping.</div><div>Recently, 11 variants in the <em>ZFX</em> gene were reported to cause a distinct X-linked neurodevelopmental disorder in 18 male patients, and a female was reported with hyperparathyroidism in concurrence with a <em>ZFX</em> variant. In this report, we present a male patient and his mother with a new likely pathogenic variant in the <em>ZFX</em> gene (NM_003410.4(<em>ZFX</em>): c.2363C &gt; G, p. Pro788Arg). The phenotype of the patient includes a global neurodevelopmental delay and several additional features greatly overlapping with the phenotype in previously described patients, including facial features, hypotonia, diminished white matter and thin corpus callosum, inguinal and umbilical herniation, and ophthalmological abnormalities. An elevated PTH was noted, with normocalcemia, a possible early sign of hyperparathyroidism. Additionally, a small colon, signs of a bleeding diathesis and a cervical swelling of non-specific origin were present, which were not reported in patients with <em>ZFX</em> variants before. The mother presents with fatigue, low iron status and a slight elevation of PTH with normocalcemia.</div><div>This report adds valuable data to the phenotypical spectrum of the <em>ZFX</em>-related neurodevelopmental disorder.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105053"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279279","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}