European journal of medical genetics最新文献

{"title":"Tailoring monogenic disease carrier screening panels for Chinese populations: The importance of considering regional differences","authors":"Wei Hou ,&nbsp;Xiaolin Fu ,&nbsp;Xiaoxiao Xie ,&nbsp;Chunyan Zhang ,&nbsp;Manli Zhang ,&nbsp;Rui Xiao ,&nbsp;Yanping Lu","doi":"10.1016/j.ejmg.2025.105002","DOIUrl":"10.1016/j.ejmg.2025.105002","url":null,"abstract":"<div><div>Carrier screening for monogenic diseases is becoming increasingly important in preventive medicine, yet selecting appropriate target genes remains a complex task, especially in countries with significant ethnic and geographic diversity such as China. This study aimed to develop a strategy to screen for carrier screening target genes suitable for the Chinese population, considering regional variations in carrier frequencies (CFs).</div><div>We analyzed a dataset from a large-scale, multicenter carrier screening study, encompassing 33,104 individuals from different regions of China and carrier status for 223 genes. We focused on the CFs of these genes across regions. The study first stratified the population based on participants' self-reported ancestral places and then applied consensus k-means clustering analysis to the CF characteristics of these regions. This approach enabled us to identify distinct regional subpopulations with shared genetic backgrounds.</div><div>The results showed that the regions clustered into three subpopulations (North, South, and Far South) based on CF characteristics, and 44 genes exhibited significant CF differences across these subpopulations (α = 0.05). Applying an overall CF threshold without considering regional diversity would have excluded 11 regionally prevalent genes from the screening panel. By incorporating regional variations, we accurately identified 58 genes that met the recommended CF criteria (autosomal gene CF &gt; 1/200, X-linked gene CF &gt; 1/40,000) in at least one subpopulation.</div><div>This study emphasizes the importance of considering regional diversity when designing carrier screening panels for monogenic diseases in China. Our proposed strategy, combining regional stratification and clustering analysis, provides a more precise method for selecting target genes, thereby enhancing the effectiveness and relevance of screening programs across different Chinese populations.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 105002"},"PeriodicalIF":1.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467406","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":"Variability in autism spectrum phenotypes linked to heterozygous missense familial ANK2 mutation","authors":"R. Garotti ,&nbsp;M. Marino ,&nbsp;M.P. Riccio ,&nbsp;G. Cappuccio ,&nbsp;V. Maffettone ,&nbsp;C. Bravaccio","doi":"10.1016/j.ejmg.2025.105001","DOIUrl":"10.1016/j.ejmg.2025.105001","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is to date considered a disorder with a complex aetiology that recognizes both genetic and environmental risk factors. The role of the genetic contribution is progressively and significantly increasing, and lately thousands of genes have been linked to ASD. In this clinical report we describe a child with ASD carrying a heterozygous novel missense variant p.Arg987Trp in the <em>ANK2</em> gene in heterozygous state, predicted pathogenic, and inherited from her father. The <em>ANK2</em> gene has been associated with ASD but to date just few reports described the related phenotypes thus we aim at expanding behaviours endophenotypes of familial <em>ANK2</em>-related condition. Our patient was diagnosed with high-functioning ASD while her father showed subthreshold autistic traits such as relational difficulties and peculiar interests. We present this familial case to study genotype-phenotype correlation and highlight the huge variability of Autism spectrum phenotypes of the <em>ANK2-</em>related conditions. Nevertheless, future studies that can explore more of the link between the genetics of autism and associated clinical expressivity would be interesting.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 105001"},"PeriodicalIF":1.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453934","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":"Co-occurring non-urinary congenital anomalies among cases with congenital anomalies of the kidney and urinary tract","authors":"Claude Stoll,&nbsp;Beatrice Dott,&nbsp;Yves Alembik,&nbsp;Marie-Paule Roth","doi":"10.1016/j.ejmg.2025.105000","DOIUrl":"10.1016/j.ejmg.2025.105000","url":null,"abstract":"<div><div>Cases with congenital anomalies of kidney and urinary tract (CAKUT) often have other associated anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in CAKUT in a well-characterized population from northeastern France. The associated anomalies in CAKUT were collected in all live births, stillbirths and terminations of pregnancy during 29 years in 387,067 consecutive births of known outcome in the area covered by our population-based registry of congenital anomalies. Of the 1946 cases with CAKUT born during this period (prevalence at birth of 50.3 per 10,000), 653 (33.6%) had associated anomalies. There were 138 (7.1%) patients with chromosomal abnormalities including 39 trisomy 18 (2%), and 195 (10%) syndromic conditions including VA(C)TER(L) association (3.3%), Meckel-Gruber syndrome (2.1%), and prune belly syndrome (1.4%). Three hundred twenty (16.4%) of the cases had multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the digestive, the cardiovascular and the central nervous systems were the most common other non urinary anomalies. Prenatal diagnosis was obtained in 71.5% of the cases with CAKUT. In conclusion the overall prevalence of associated anomalies, which was one out of three cases, emphasizes the need for a thorough investigation of cases with CAKUT. A routine screening for other non urinary anomalies may be considered in cases with CAKUT. One should be aware that the non urinary anomalies associated with CAKUT can be classified into a recognizable anomaly syndrome or pattern in one out of six cases with CAKUT.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 105000"},"PeriodicalIF":1.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413653","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":"Cardiogenetics and uncertainty: Evaluation of professional vulnerability in France","authors":"Lea Gaudillat ,&nbsp;Lea Patay ,&nbsp;Caroline Sawka ,&nbsp;Amandine Baurand ,&nbsp;Sophie Nambot ,&nbsp;Camille Level ,&nbsp;Gabriel Laurent ,&nbsp;Jean-Christophe Eicher ,&nbsp;Geraldine Bertaux ,&nbsp;Sylvie Falcon Eicher ,&nbsp;Charlotte Denis ,&nbsp;Sarah Carvallo ,&nbsp;Cécile Cazeneuve ,&nbsp;Alexandre Janin ,&nbsp;Gilles Millat ,&nbsp;Christine Peyron ,&nbsp;Christel Thauvin-Robinet ,&nbsp;Philippe Charron ,&nbsp;Laurence Faivre","doi":"10.1016/j.ejmg.2025.104999","DOIUrl":"10.1016/j.ejmg.2025.104999","url":null,"abstract":"<div><div>Scientific advances in genomics are transforming healthcare and prevention. However, they also increase situations of uncertainty, which in turn increase vulnerability not only for patients and their families but also for professionals. Cardiogenetics plays a crucial role in preventing sudden death in young individuals, but it can pose complex challenges for healthcare teams. To study professionals' perspectives and experiences regarding cardiogenetics-related vulnerability, a national online survey was conducted in France to gather insight from professionals involved in the care pathway of individuals with cardiogenetic conditions. The survey targeted clinical geneticists, genetic counselors, cardiologists, nurses, and psychologists, in collaboration with the CARDIOGEN network.</div><div>Out of 86 respondents, the majority (64%) reported experiencing vulnerability, which was not correlated with their profession, experience, or the organization of their clinics. Acknowledged vulnerabilities were mainly related to uncertainties regarding incomplete penetrance, variable expression, and genotype-phenotype disparities in cardiogenetics, exacerbated by the evolving interpretation of genetic data, due to the increased access to genomics. Additionally, the implications of these issues, particularly in cases of unexplained sudden deaths that necessitated genetic investigations and family follow up recommendations, raised further concerns. The reported vulnerabilities encompassed both the need for specialized knowledge and the structural complexities of teams combining skills in genetics and cardiology. In addition, the professionals’ capacity to empathize can add a degree of vulnerability. Finally, it seems important to focus on how cardiogenetics teams are organized, particularly through close collaboration among genetics and cardiology units, which could help reduce this feeling of vulnerability.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 104999"},"PeriodicalIF":1.6,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398634","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 KDM5C variant corrects a previously erroneous diagnosis","authors":"Julia Chapin ,&nbsp;Bekim Sadikovic ,&nbsp;Jennifer Kerkhof ,&nbsp;Charles E. Schwartz ,&nbsp;Roger E. Stevenson ,&nbsp;Cindy Skinner ,&nbsp;Melanie May ,&nbsp;Michael Friez ,&nbsp;Robert Roger Lebel","doi":"10.1016/j.ejmg.2025.104997","DOIUrl":"10.1016/j.ejmg.2025.104997","url":null,"abstract":"<div><div>Over two decades ago, a primigravid female presented with concern for recurrence of an adverse phenotype affecting her three brothers. The three brothers presented with intellectual disability, developmental delay, behavior problems and dysmorphic features. The screening tools available at the time revealed an <em>FGD1</em> variant present in all three brothers, their mother being a carrier, absent in their unaffected uncle, and absent in the proband herself. This variant was hypothesized to be explanatory, but years later more advanced genetic screening showed that it was benign. Episign analysis revealed the true cause, a novel pathogenic <em>KDM5C</em> variant. This case study provides further insight into the <em>KDM5C</em> phenotype and demonstrates the importance of amending past errors as science evolves.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 104997"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122607","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":"Improved variant detection using long-read sequencing and optical mapping: Illustration in STRC-related hearing loss","authors":"Sacha Laurent ,&nbsp;Anne Vannier ,&nbsp;Corinne Gehrig ,&nbsp;Marc Abramowicz ,&nbsp;Ariane Paoloni-Giacobino ,&nbsp;Hélène Cao Van ,&nbsp;Michel Guipponi","doi":"10.1016/j.ejmg.2024.104986","DOIUrl":"10.1016/j.ejmg.2024.104986","url":null,"abstract":"<div><div>Biallelic loss-of-function variants in <em>STRC</em> contribute to mild-moderate hearing loss (DFNB16). Here, we report a female patient with mild hearing loss. Exome sequencing and MLPA analysis revealed <em>STRC</em> biallelic inactivation due to a nonsense and a <em>CKMT1B</em>-<em>STRC</em> deletion. Analysis of the self-reported normal-hearing parents revealed inconsistent <em>M</em><em>endelian</em> inheritance. Indeed, the mother was a heterozygous carrier of a <em>CKTM1B-STRC-CATSPER2</em> deletion, and the father shared the same genotype as his daughter. He was later found to also have mild-moderate hearing loss.</div><div>To address these discrepancies, we used long-read sequencing and optical genome mapping. We demonstrated that the father, in fact, carried a <em>CKMT1B-STRC-CATSPER2</em> deletion in trans with the <em>STRC</em> nonsense variant and a tandem duplication of <em>CATSPER2-CKMT1A</em>. The proband inherited this latter haplotype, together with the maternal <em>CKMT1B-STRC-CATSPER2</em> deletion.</div><div>Combining these two technologies allowed us to fully elucidate the complex structural rearrangements at the <em>STRC</em> locus and provide appropriate genetic counselling.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"73 ","pages":"Article 104986"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791349","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":"CHD3-related Snijders Blok-Campeau syndrome with Spastic Paraplegia, Ataxia, and Situs Inversus","authors":"Lin Chen,&nbsp;Yanjiao Bu,&nbsp;Yuwen Yu,&nbsp;Yongxing Chen,&nbsp;Xiaoguang Lei","doi":"10.1016/j.ejmg.2024.104988","DOIUrl":"10.1016/j.ejmg.2024.104988","url":null,"abstract":"<div><div>The Chromodomain Helicase DNA-binding (CHD) protein family is ATP-dependent chromatin remodeling proteins that utilize energy produced by ATP hydrolysis to regulate chromatin structure and thereby modulate gene expression. The earliest report of a <em>CHD3</em> gene mutation was by O'Roak, who found it during whole exome sequencing of 189 autism families in 2012. In 2018, Snijders Blok systematically assessed the autosomal dominant neurodevelopmental disorder caused by <em>CHD3</em> gene damage, known as Snijders Blok-Campeau syndrome (SNIBCPS, OMIM <span><span>618205</span><svg><path></path></svg></span>). Its typical features include global developmental delay, speech delay, mild to severe intellectual disability, hypotonia, autism, and distinctive facial features such as macrocephaly (microcephaly in minority), prominent forehead and so on. This article reports a patient of slow speech, intellectual disability, epilepsy, spastic paraplegia, ataxia and situs inversus with a <em>CHD3</em> gene mutation. The features of spastic paraplegia, ataxia, and situs inversus have not been reported previously. In conclusion, <em>CHD3</em> gene mutations represent a rare disease with diverse clinical phenotypic features. This patient contributes valuable insights into the understanding of <em>CHD3</em> gene mutation manifestations, expanding the scope beyond previously reported features.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"73 ","pages":"Article 104988"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871707","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":"Brain calcification in congenital heart defects and ectodermal dysplasia (CHDED)","authors":"Daisuke Watanabe ,&nbsp;Yohei Hasebe ,&nbsp;Hideaki Yagasaki ,&nbsp;Daisuke Nakato ,&nbsp;Mamiko Yamada ,&nbsp;Hisato Suzuki ,&nbsp;Yosuke Kono ,&nbsp;Yuto Sunaga ,&nbsp;Masashi Yoshizawa ,&nbsp;Hiromune Narusawa ,&nbsp;Fuyuki Miya ,&nbsp;Toshiki Takenouchi ,&nbsp;Takeshi Inukai ,&nbsp;Kenjiro Kosaki","doi":"10.1016/j.ejmg.2024.104992","DOIUrl":"10.1016/j.ejmg.2024.104992","url":null,"abstract":"<div><div>Congenital Heart Defect and Ectodermal Dysplasia (CHDED) is an autosomal dominant disorder caused by the <em>PRKD1</em> gene. CHDED is characterized by heart defects and ectodermal dysplasia. To date, eight patients with CHDED have been described. Calcifications were present in three patients with CHDED. (two patients; renal calcifications, one patient; brain calcifications). The organ distribution of calcifications in CHDED has been unclear. We report here another patient with CHDED and brain calcifications. The patient was a 9-month-old Japanese girl. She presented with heart defects and ectodermal dysplasia. At 6 months of age, she had generalized seizures, and a CT scan revealed calcifications in the bilateral deep cerebral white matter. The seizures resolved with the administration of levetiracetam. The patient had a de novo, heterozygous pathogenic variant, c.1808G &gt; A, p.(Arg603His), in the <em>PRKD1</em> gene. Together with the previously reported patients mentioned above, we demonstrated the role of the <em>PRKD1</em> variant in brain calcification. We propose that <em>PRKD1</em> and two genes, <em>ITGB2</em> and <em>JAM2</em>, which are known to be associated with brain calcification, act through a common signaling pathway abnormality. In support of our hypothesis, there are some experimental results that link PRKD1 and JAM2. PRKD1 functions with the integrin ITGB2 as a partner. JAM2, which is associated with brain calcification and is critical for maintaining of the tight junction of the endothelial cells, interacts with integrins including ITGB2. Therefore, PRKD1 could lead to the pathological phenotype of brain calcification.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"73 ","pages":"Article 104992"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909586","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":"Promoting reflective practice: Exploring access to supervision in European genetic counselling programmes","authors":"Inês Costa ,&nbsp;Lídia Guimarães ,&nbsp;Milena Paneque","doi":"10.1016/j.ejmg.2025.104998","DOIUrl":"10.1016/j.ejmg.2025.104998","url":null,"abstract":"<div><div>Genetic Counselling Supervision (GCS) plays an integral role in professional development, stimulating reflective practice and helping to prevent burnout. Nevertheless, evidence points to insufficient practice of GCS. This study aimed to explore the current state of counselling supervision access during MSc training, along with barriers and facilitators for its implementation. MSc coordinators of the current EBMG accredited programmes were invited to participate in this study via email, with the request to fill out a questionnaire. The qualitative data obtained was reviewed using thematic analysis, while descriptive statistics was used for the quantitative data.</div><div>GCS was considered crucial for fostering professional development, safe practice, and emotional support for the future professionals.</div><div>While all MSc programmes included counselling supervision in their course curricula, its implementation was highly heterogeneous. Students have access to GCS during clinical placements in 62,5% of the programmes, facilitated by institutional support and EBMG guidelines. Several barriers hindered its broader implementation, as was the case of a shortage of senior genetic counsellors and the lack of professional recognition in some countries.</div><div>This study compiled evidence of the insufficient practice of GCS across Europe and its limited integration in MSc programmes. Therefore, we recommend educational pathways actively promote genetic counselling supervision routines to ensure graduates enter the workforce with the necessary tools to provide care with the expected standard of safety and quality, while maintaining a reflective practice.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"74 ","pages":"Article 104998"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122068","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":"Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe","authors":"Shauna Quinn ,&nbsp;Nicola Walsh ,&nbsp;Ioana Streata ,&nbsp;Athina Ververi ,&nbsp;Samarth Kulshrestha ,&nbsp;Ratna Dua Puri ,&nbsp;Anca Lelia Riza ,&nbsp;Aoibhinn Walsh ,&nbsp;Kathleen Gorman ,&nbsp;Ellen Crushell ,&nbsp;Andrew Green ,&nbsp;Janna Kenny ,&nbsp;Sally Ann Lynch","doi":"10.1016/j.ejmg.2024.104989","DOIUrl":"10.1016/j.ejmg.2024.104989","url":null,"abstract":"<div><h3>Background</h3><div>The Roma population are an endogamous, genetically isolated, minority population who migrated from North-Western India to Europe from the 10th Century throughout the Byzantine period and continues to the present day. Approximately 10–12 million Romani people reside in segregated settlements in Europe, and smaller populations live in North America and China. In addition to the endogamy, they also practice consanguinity. This has resulted in a higher frequency of rare autosomal recessive disorders some of which are unique to the Roma population. Some disorders result from founder variants whilst others are private variants, occurring within one nuclear family. Most are found as homozygous variants but compound heterozygosity is seen in a number of conditions.</div></div><div><h3>Objective</h3><div>Clinicians and scientists with experience in managing and diagnosing rare diseases in this population in Ireland, Romania and Greece have developed a comprehensive catalogue of autosomal recessive inherited disorders found in the Roma population. Our aim is that this catalogue will aid rapid diagnosis and highlight the differential diagnoses to consider in challenging cases.</div></div><div><h3>Methods</h3><div>We performed a detailed literature search to identify relevant publications and disease variants described in patients whose ethnicity was described as Roma. In addition, we interrogated data from local clinicians and colleagues in Ireland and Romania to collect additional unpublished variants which have yet to be reported in the medical literature. Where possible, we have mapped these disorders back to their European country of origin. Furthermore, we searched the variants allele frequencies on ClinVar. We analysed exome data from New Delhi, India to trace any of these founder variants back their origins.</div></div><div><h3>Results</h3><div>We identified 90 distinct autosomal recessive disorders, manifesting as 91 distinct phenotypes and 111 pathogenic disease variants. These include both published (n = 91) and unpublished (n = 20) findings identified in the Roma population in Europe. The Indian exome data revealed that only 12/111 variants were identified.</div></div><div><h3>Conclusion</h3><div>We have assembled a catalogue of inherited autosomal recessive disorders and 111 pathogenic variants found in the Roma population. We hope that this will assist the medical and scientific community to make prompt diagnoses and consider adaptation of a targeted genetic approach to facilitate timely and cost-effective diagnoses in this population.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"73 ","pages":"Article 104989"},"PeriodicalIF":1.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871706","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}