European journal of medical genetics最新文献

{"title":"Genetic susceptibility in Takotsubo syndrome: a candidate gene association analysis in the French TAKOGENE cohort.","authors":"Laury Nicolas, Sophie Garnier, Edouard Gerbaud, Franck Paganelli, Denis Doyen, Pascal Motreff, Patrick Meimoun, Erwan Donal, Vincent Probst, Grégory Ducrocq, Jean-François Aupetit, Ariel Cohen, Christophe Tribouilloy, Olivier Nallet, Nicolas Lamblin, Damien Logeart, Frédéric Moulin, Eric Durand, Olivier Varenne, Pascal Lim, Taing Lieng, Robert Olaso, Doris Lechner, Jean-François Deleuze, Philippe Charron, Nicolas Mansencal","doi":"10.1016/j.ejmg.2026.105108","DOIUrl":"https://doi.org/10.1016/j.ejmg.2026.105108","url":null,"abstract":"<p><p>Takotsubo syndrome (TTS) is a stress-induced left ventricular (LV) cardiomyopathy with an unclear genetic predisposition. We investigated whether single nucleotide polymorphisms (SNPs) previously associated with other cardiomyopathies or LV physiological traits contribute to TTS susceptibility. We conducted a case-control study based on the French multicentre TAKOGENE study (NCT01520610), including 261 unrelated TTS patients and 259 sex- and age-matched controls presenting with acute coronary syndrome. All participants were of European ancestry. A total of 325 SNPs were selected from large-scale genome-wide association studies of cardiomyopathies (n=202) and LV structural/functional traits (n=123), derived from polygenic risk scores. Genotyping was performed using the Infinium OmniExpressExome-8 array. Associations were assessed by logistic regression under an additive model, adjusted for age and sex, with group-specific Bonferroni correction. A sensitivity analysis compared the 261 TTS cases with 973 French population controls from the EPP3 cohort. After quality control and statistical analysis, seventeen SNPs (nine related to cardiomyopathies and eight to LV traits) showed nominal associations (P < 0.05), but none remained significant after group-specific Bonferroni correction. The strongest signal was observed for rs6885658 in the CPEB4 gene (OR 1.62, 95% CI 1.23-2.15; P = 5.8 × 10^-4) related to cardiomyopathy traits. The EPP3 population-control sensitivity analysis was consistent with the primary analysis, with no association remaining significant after correction. In conclusion, common genetic variants previously associated with cardiomyopathies or LV traits do not appear to have a major effect on TTS risk. These findings support a disease-specific polygenic architecture of TTS, distinct from that underlying chronic cardiomyopathies and baseline LV traits. Future studies should explore alternative approaches, such as pathway-based analyses focusing on stress-response mechanisms.</p>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":" ","pages":"105108"},"PeriodicalIF":2.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165691","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":"Developing consensus on rare disease care pathways and ERN integration across Europe: insights from stakeholder workshops and a Delphi study","authors":"Augutė Juozapavičiūtė-Dvinelė,&nbsp;Michel W.P. Tsang-A-Sjoe,&nbsp;Madara Auzenbaha,&nbsp;Karolis Ažukaitis,&nbsp;Birutė Tumienė","doi":"10.1016/j.ejmg.2026.105096","DOIUrl":"10.1016/j.ejmg.2026.105096","url":null,"abstract":"<div><h3>Background</h3><div>Rare disease care pathways are complex and require coordination among specialised and non-specialised services, including genetic diagnostics, multidisciplinary expertise, and cross-border collaboration. Despite increasing policy attention and the establishment of European Reference Networks, the development and implementation of cohesive rare disease care pathways remain inconsistent across Europe. A shared, consensus-based framework reflecting stakeholder priorities is needed.</div></div><div><h3>Methods</h3><div>This exploratory study combined structured stakeholder workshops and a Delphi consensus process. Nine workshops were conducted within the JARDIN project, engaging stakeholders from 16 European countries. Data were collected using standardised Miro boards and analysed thematically using MAXQDA, guided by the SEIPS 2.0 framework. Insights from this analysis informed the development of statements, which were evaluated through a Delphi survey. Consensus was predefined as a median score of at least 4, an interquartile range (IQR) ≤1, and ≥80% agreement (ratings 4–5).</div></div><div><h3>Results</h3><div>A total of 216 individuals participated in the workshops, of whom 164 contributed during live sessions. Workshop data generated 1767 entries mapped across SEIPS domains. Seven thematic areas were identified: national strategy and governance; financing and sustainability; organisational structures and care coordination; access and equity; digital infrastructure and data systems; capacity building and education; and patient empowerment. Eighty-eight participants completed the Delphi survey, and consensus was achieved on all statements in the first round.</div></div><div><h3>Conclusion</h3><div>The findings demonstrate strong cross-country agreement on system-level requirements for effective rare disease care pathways. These consensus statements provide a structured framework for developing national care pathways and integrating European Reference Networks activities into routine healthcare systems.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"83 ","pages":"Article 105096"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683852","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 de novo CACNA1G variant p.(Arg1553Gln) associated with neurodevelopmental delay and cerebellar hypoplasia: Expanding the phenotypic spectrum","authors":"Ayberk Selek,&nbsp;Furkan Orpay,&nbsp;Bülent Unay","doi":"10.1016/j.ejmg.2026.105088","DOIUrl":"10.1016/j.ejmg.2026.105088","url":null,"abstract":"<div><div>CACNA1G encodes the Cav3.1 T-type calcium channel, a key regulator of neuronal excitability and thalamocortical rhythmicity. Pathogenic variants have been associated with neurodevelopmental disorders, frequently accompanied by epilepsy and cerebellar abnormalities. We report a patient with global developmental delay and autism spectrum disorder who developed progressive gait instability and was found to harbor a novel de-novo CACNA1G variant, c.4658G &gt; A p.(Arg1553Gln). Notably, the patient had no history of seizures and normal electroencephalographic findings. Brain magnetic resonance imaging revealed cerebellar and vermian hypoplasia, consistent with previously described cases, as well as an incidental intracranial lipoma. Distinctive clinical features included macrocephaly and appendicular hypertonia, findings not previously reported in association with CACNA1G-related disorders and potentially expanding the phenotypic spectrum. The identified variant is located in the intracellular III–IV linker region of Cav3.1, outside the canonical pore-forming domains where most epilepsy-associated variants cluster. Its absence from the literature and public variant databases supports its novelty. This case broadens the clinical and molecular spectrum of CACNA1G-related disease and highlights phenotypic variability, particularly in patients without epilepsy.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"82 ","pages":"Article 105088"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270831","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":"New insights into the complex genetic architecture of age-related hearing loss","authors":"Crystel Bonnet,&nbsp;Salim Aiche,&nbsp;Sophie Boucher","doi":"10.1016/j.ejmg.2026.105089","DOIUrl":"10.1016/j.ejmg.2026.105089","url":null,"abstract":"<div><div>Age-related hearing loss (ARHL), or presbycusis, is a very common sensory disorder resulting from cumulative exposure to environmental factors, biological aging and a significant genetic component. Although most cases of ARHL result from the combined influence of numerous low-effect variants, the increasing number of monogenic forms has shown the importance of rare, highly penetrant mutations in ARHL. Advances in whole-exome and whole-genome sequencing have strengthened the evidence for monogenic contributions, identifying deleterious variants consistent with dominant, recessive, or mitochondrial inheritance patterns. These monogenic cases provide valuable insights into the molecular mechanisms underlying cochlear aging and the vulnerability of sensory cells. To date, several genes have been clearly identified as responsible for familial or sporadic late-onset hearing loss, including <em>KCNQ4</em>, <em>GRHL2</em>, <em>ILDR1</em>, <em>EYA4</em>, <em>MYO6</em>, <em>MYO7A</em>, <em>TECTA</em>, <em>WFS1</em>, <em>CDH23</em>, and <em>TMC1</em>. Mutations in these genes affect diverse biological pathways such as potassium recycling, epithelial integrity, transcriptional regulation, mechanotransduction, extracellular matrix stability, and hair cell maintenance—functions that are fundamental to the long-term preservation of hearing. It is important to note that there is a growing overlap between the genes involved in Mendelian deafness and the susceptibility loci identified in ARHL, suggesting the existence of common molecular mechanisms between early-onset hereditary deafness and some forms of progressive ARHL. Furthermore, new data highlight the role of epigenetic regulation, mitochondrial dysfunction, cochlear synaptopathy, and non-coding RNAs in hearing loss. Despite major advances, several challenges remain, including phenotypic heterogeneity, limited representation of non-European populations, and a lack of consistency in the reproducibility of results across studies. Distinguishing between subtypes of ARHL characterized by audiometry—including sensory, neural and synaptopathic, metabolic forms, will likely be essential for improving genetic analyses and precision medicine approaches. Moreover, although polygenic risk scores (PRS) represent a promising strategy for risk prediction, their clinical applicability remains limited. Overall, the integration of monogenic, polygenic, environmental, and epigenetic data will be essential for understanding the complex genetic architecture of ARHL and for developing future personalized therapeutic interventions.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"82 ","pages":"Article 105089"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360006","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":"Development of a predictive matrix for pre-test genetic counselling in inherited retinal diseases based on data from 1001 patients enrolled in the IRD-PT registry","authors":"Inês Figueiredo,&nbsp;Nuno Cruz,&nbsp;Beatriz Gaspar,&nbsp;Nuno Gouveia,&nbsp;Pedro Moreira Martins,&nbsp;Sara Geada,&nbsp;Rufino Silva,&nbsp;Ana Luísa Carvalho,&nbsp;João Pedro Marques","doi":"10.1016/j.ejmg.2026.105087","DOIUrl":"10.1016/j.ejmg.2026.105087","url":null,"abstract":"<div><div>Genetic testing plays a pivotal role in the management of Inherited Retinal Diseases (IRDs), yet a significant proportion of patients remain without a molecular diagnosis. This study aimed to develop a predictive matrix to estimate the likelihood of diagnostic success in order to manage patient expectations prior to genetic testing. Conducted as a retrospective, single-center cohort study, it analyzed data from 1001 IRD patients across 804 unrelated families enrolled in the IRD-PT registry. Key clinical variables—including age at symptom onset, family history, consanguinity, and referral timing—were evaluated for their association with genetic diagnostic yield. Results showed that 68.03% of families received a solved diagnosis, while 11.19% were likely solved. The presence of consanguinity, a positive family history, or childhood symptom onset significantly increased the probability of a solved diagnosis (up to 81.7%), whereas their absence reduced it to 31.2%. The study culminated in the creation of a conditional probability model that stratifies patients by their likelihood of molecular confirmation. This tool offers clinicians a practical, evidence-based approach to pre-test genetic counselling, enhancing transparency and expectation management for patients undergoing IRD genetic testing.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"82 ","pages":"Article 105087"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263811","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":"Hearing outcomes after cochlear implantation in two patients with ATP6V1B2-related deafness and onychodystrophy","authors":"Sarah Chamieh,&nbsp;Pauline Marzin,&nbsp;Sophie Achard,&nbsp;Pierre Blanc,&nbsp;Laurence Jonard,&nbsp;Saba Battelino,&nbsp;Katarina Trebusak,&nbsp;Margaux Serey-Gaut,&nbsp;Sandrine Marlin","doi":"10.1016/j.ejmg.2026.105090","DOIUrl":"10.1016/j.ejmg.2026.105090","url":null,"abstract":"<div><div>The gold standard recommendation for congenital sensorineural hearing loss (SNHL) care is cochlear implantation (CI). Adjusting for confounding factors such as developmental comorbidities is crucial when assessing expected outcomes of the procedure for the patients, their families, and their medical teams. We describe two clinical cases of the deafness and onychodystrophy (DOD) spectrum and the benefit of molecular diagnosis to underline the importance of genetic testing when evaluating potential CI outcomes in syndromic congenital SNHL.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"82 ","pages":"Article 105090"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337946","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":"Clinical and genetic spectrum of trichorhinophalangeal syndrome type I/III in 20 children of Korean origin","authors":"Ayoung Park,&nbsp;Naye Choi,&nbsp;Tae-Joon Cho,&nbsp;Jung Min Ko","doi":"10.1016/j.ejmg.2026.105091","DOIUrl":"10.1016/j.ejmg.2026.105091","url":null,"abstract":"<div><h3>Background</h3><div>Trichorhinophalangeal syndrome type I/III (TRPS I/III) is a rare autosomal dominant skeletal dysplasia caused by pathogenic variants of <em>TRPS1</em>. Although several European cohorts have been reported, data from East Asian populations remain limited and longitudinal growth patterns and treatment responses have not been systematically evaluated.</div></div><div><h3>Methods</h3><div>We conducted a retrospective single-center study of 20 unrelated children of Korean origin with molecularly confirmed TRPS I/III, between 2012 and 2024. The clinical, radiological, and genetic data were reviewed. Growth parameters were analyzed using Korean reference standards and genotype–phenotype correlations were explored. Treatment responses to recombinant human growth hormone (rhGH) and minoxidil were assessed descriptively.</div></div><div><h3>Results</h3><div>All the patients exhibited characteristic craniofacial features and cone-shaped epiphyses with variable skeletal involvement. Short stature (standard deviation score [SDS] of height &lt; −2) was observed in 21% of patients. Bone age was delayed before 12 years of age but showed rapid advancement thereafter, accompanied by a decline in height SDS during adolescence <em>(p = 0.017</em>). Truncating variants were identified in 65% of patients, missense variants in exon 6 in 15%, and exonic deletions in 20%. Missense variants in exon 6 were consistently associated with severe brachydactyly, whereas the overall stature showed no clear correlation with genotype. Responses to rhGH and minoxidil treatments were variable.</div></div><div><h3>Conclusions</h3><div>TRPS I/III demonstrated substantial phenotypic heterogeneity and age-dependent growth dynamics in this Korean cohort. Severe distal limb involvement was associated with exon 6 missense variants, whereas growth impairment remained variable. Long-term follow-up and multidisciplinary management are essential to optimize clinical outcomes.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"82 ","pages":"Article 105091"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337993","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":"MMP13-related Metaphyseal anadysplasia type 1 presenting with rickets-like manifestations in a family","authors":"Sofia Thunström ,&nbsp;Pavel Antonsson ,&nbsp;Simon Stenberg ,&nbsp;Emelie E. Aspholm ,&nbsp;Diana Swolin Eide","doi":"10.1016/j.ejmg.2026.105080","DOIUrl":"10.1016/j.ejmg.2026.105080","url":null,"abstract":"<div><h3>Background</h3><div>Metaphyseal anadysplasia 1, which includes Spondyloepimetaphyseal dysplasia Missouri type, is a rare autosomal dominant skeletal dysplasia characterized by short stature, mild limb deformities, and transient metaphyseal irregularities that typically resolve with age. The condition is caused by heterozygous missense variants in the <em>MMP13</em> gene, encoding matrix metalloproteinase 13, a key enzyme in endochondral ossification and extracellular matrix remodeling. Pathogenic variants in <em>MMP13</em> are exceedingly rare, with only a few families reported.</div></div><div><h3>Case presentation</h3><div>We report two siblings, aged 3 and 1 years, in Sweden, presenting with clinical and radiological features consistent with Metaphyseal anadysplasia 1. Their father, of Syrian origin, exhibited short stature and mild femoral bowing. Genetic analysis revealed a novel heterozygous missense variant c.217T &gt; C, p.(Ser73Pro) in <em>MMP13</em>, inherited from the affected father, and located within the same <em>MMP13</em> domain as previously reported patients. The family pedigree demonstrates multiple affected individuals with short stature and bowed femurs, consistent with autosomal dominant inheritance. Radiographic imaging of father confirmed persistent but mild skeletal abnormalities.</div></div><div><h3>Conclusion</h3><div>This report expands the genotypic spectrum of Metaphyseal anadysplasia 1 and suggests a putative mutational hotspot in exon 2. It further emphasizes the importance of thorough clinical, radiological, and genetic evaluation in families with short stature and metaphyseal irregularities and a clinical long-term follow-up is proposed with regular radiographic monitoring.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"81 ","pages":"Article 105080"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802850","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":"Thoracic chordoma following intracranial meningioma in a patient with a novel germline SMARCE1 variant","authors":"Takao Tsurubuchi ,&nbsp;Yuni Yamaki ,&nbsp;Hiroko Fukushima ,&nbsp;Kosuke Sato ,&nbsp;Hiroshi Takahashi ,&nbsp;Hiroki Karita ,&nbsp;Noriaki Sakamoto ,&nbsp;Masashi Mizumoto ,&nbsp;Kei Nakai ,&nbsp;Hideyuki Sakurai ,&nbsp;Ai Muroi ,&nbsp;Masahide Matsuda ,&nbsp;Hidetoshi Takada ,&nbsp;Eiichi Ishikawa","doi":"10.1016/j.ejmg.2026.105068","DOIUrl":"10.1016/j.ejmg.2026.105068","url":null,"abstract":"<div><div>Paediatric cancer predisposing factors (CPFs), such as DICER1 syndrome, Li-Fraumeni syndrome, and SMARC-related syndromes, are increasingly being identified through genome-wide sequencing of surgical specimens. Among these, mutations in the SWItch/Sucrose Non-Fermentable chromatin-remodelling complex, particularly involving the <em>SMARCE1</em> gene, have been implicated in various paediatric tumours, including clear cell meningioma (CCM). However, the role of <em>SMARCE1</em> mutations in other rare tumours like chordoma remains undetermined. <em>TBXT</em> is a gain-of-function driver mutation of chordoma alongside upregulated <em>transforming growth factor beta 1</em> (<em>TGFβ1</em>) and <em>epidermal growth factor receptor</em> (<em>EGFR</em>). Herein, we report a rare case of thoracic chordoma with sudden abdominal pain after treatment for intracranial CCM. Germline analyses of surgical specimens from CCM and chordoma showed heterozygous mutations in both the <em>SMARCE1</em> (chromosome 17q21.2) and <em>TBXT</em> (brachyury, chromosome 6q27) genes. Somatic mutation analyses showed loss of heterozygosity at the <em>SMARCE1</em> gene region in both CCM and chordoma surgical specimens, as well as at the <em>TBXT</em> gene region in CCM, but not in chordoma. We speculated that both <em>TBXT</em> and <em>SMARCE1</em> might indirectly promote <em>EGFR</em> signalling to drive chordoma cell proliferation and survival, although the direct interaction between <em>TBXT</em> and <em>SMARCE1</em> is unknown. To our knowledge, this is the first report of a patient with a spinal chordoma after CCM treatment, suggesting that <em>SMARCE1</em> is a candidate pathological factor in chordoma.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"80 ","pages":"Article 105068"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994297","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":"Neonatal erythroderma and immunodysplasia: Overlap of cartilage-hair hypoplasia and Omenn syndrome","authors":"Anna Insalaco ,&nbsp;Cecilia Rossi ,&nbsp;Emma Bertucci ,&nbsp;Chiara Fiorentini ,&nbsp;Annarosa Soresina ,&nbsp;Silvia Giliani ,&nbsp;Fulvio Porta ,&nbsp;Alberto Berardi ,&nbsp;Licia Lugli","doi":"10.1016/j.ejmg.2026.105069","DOIUrl":"10.1016/j.ejmg.2026.105069","url":null,"abstract":"<div><div>Cartilage hair hypoplasia (CHH) syndrome (OMIM #<span><span>250250</span><svg><path></path></svg></span>) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hypotrichosis and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases, and predisposition to malignancies.</div><div>CHH results from homozygous or compound heterozygous mutations in the <em>RMRP</em> gene on chromosome 9p13, which encodes an untranslated RNA component of mitochondrial RNA‐processing endoribonuclease.</div><div><em>RMRP</em> pathogenic variants can also lead to Omenn Syndrome (OS) (OMIM #<span><span>603554</span><svg><path></path></svg></span>), a systemic inflammatory condition displaying neonatal erythroderma and immunodeficiency.</div><div>This report highlights the genotypic and phenotypic overlap between CHH and OS, by presenting a newborn with skeletal dysplasia, immunodeficiency and neonatal onset erythroderma, carrying the homozygous NR_003051:n.35C &gt; A variant in the RMRP gene.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"80 ","pages":"Article 105069"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092544","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}