European journal of medical genetics最新文献_第3页

Epileptic seizures and EEG findings in 3p deletion syndrome involving SLC6A1 涉及SLC6A1的3p缺失综合征的癫痫发作和脑电图表现

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-06-13 DOI: 10.1016/j.ejmg.2025.105027

Saori Oguri, Masanori Inoue, Osamu Kobayashi, Maeda Tomoki, Kenji Ihara

{"title":"Epileptic seizures and EEG findings in 3p deletion syndrome involving SLC6A1","authors":"Saori Oguri, Masanori Inoue, Osamu Kobayashi, Maeda Tomoki, Kenji Ihara","doi":"10.1016/j.ejmg.2025.105027","DOIUrl":"10.1016/j.ejmg.2025.105027","url":null,"abstract":"<div><div>3p Deletion syndrome is a rare genetic disorder characterized by intellectual disability, growth delay, hypotonia, and distinctive facial features, with considerable phenotypic variability. Previous reports have highlighted the significance of deletions within the 3p25.3 region contributing to the development of Angelman-like features, such as stereotypic movements, a happy demeanor, epilepsy, and characteristic electroencephalogram (EEG) patterns. This study analyzed 22 patients of 3p deletion syndrome, focusing on epilepsy and EEG findings. A newly defined short smallest region of overlap (sSRO) within 3p25.3, encompassing approximately 52 kb and partially including SLC6A1 and SLC6A11, was associated with Angelman-like features, particularly epilepsy and EEG patterns. Patients with sSRO deletions exhibited a high incidence of seizures (60 %), characterized by myoclonic or absence seizures, with EEG showing generalized high-amplitude slow waves. In contrast, larger deletions beyond the sSRO were linked to dysmorphological features of 3p-syndrome, generalized tonic-clonic seizure, and non-specific EEG findings. These findings suggest that SLC6A1 dysfunction contributes to epilepsy and EEG abnormalities, possibly via impaired GABA transport, whereas patients with larger or non-overlapping deletions exhibited more typical 3p-syndrome features, suggesting that multiple neurological genes in the broader deletion region may independently contribute to more severe neurological phenotypes. In conclusion, it is important to consider GABA-related disorders, including a specific chromosomal abnormality known as 3p-syndrome with a microdeletion in the SRO region, when observing characteristic epilepsy and EEG findings resembling Angelman syndrome.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105027"},"PeriodicalIF":1.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel RORA genetic variant associated with early-onset obesity and insomnia 一种新的RORA基因变异与早发性肥胖和失眠相关。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-06-12 DOI: 10.1016/j.ejmg.2025.105028

Alexie Ouellette , Eric P. Allain , Abdullah Almaghraby , Dominique Bouhamdani , Mouna Ben Amor

引用次数: 0

Clinical variability in individuals with ATR-X syndrome in the Netherlands 荷兰ATR-X综合征患者的临床变异性

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-06-06 DOI: 10.1016/j.ejmg.2025.105026

Anne Noordhuis-Zijderveld , Dederieke A.M. Festen , Arooj Kharl , Marloes van Gastel , Madeleine Hartman , Hennie T. Bruggenwirth , Shimriet Zeidler , Marlies J. Valstar

{"title":"Clinical variability in individuals with ATR-X syndrome in the Netherlands","authors":"Anne Noordhuis-Zijderveld , Dederieke A.M. Festen , Arooj Kharl , Marloes van Gastel , Madeleine Hartman , Hennie T. Bruggenwirth , Shimriet Zeidler , Marlies J. Valstar","doi":"10.1016/j.ejmg.2025.105026","DOIUrl":"10.1016/j.ejmg.2025.105026","url":null,"abstract":"<div><h3>Background</h3><div>The Alpha Thalassemia mental Retardation syndrome, X-linked (ATR-X syndrome, MIM: 301040) is a rare genetic disorder characterized by alpha thalassemia, intellectual disability, peculier facial characteristics and genital abnormalities. Detailed information regarding the clinical phenotype is lacking.</div></div><div><h3>Aims</h3><div>Detailed descriptions of the clinical phenotype are rare. The aim of this study was to describe the clinical phenotype of ATR-X syndrome.</div></div><div><h3>Methods</h3><div>Data was collected through questionnaires, interviews, physical examination and the study of medical records.</div></div><div><h3>Results</h3><div>Twenty-two individuals, aged 2–68 years old, were included. Three individuals were deceased at the time of the study. The individuals had a variable degree of intellectual disability. Alpha thalassemia was found in 30 % and genital anomalies in 70 % of the individuals. First clinical signs of the syndrome were most frequently feeding problems, started in the neonatal period in the majority. Other main reported health problems were reflux (59 %), constipation (72 %), periods of anorexia and adipsia (45 %), heart defects (28 %), epilepsy (33 %), scoliosis/kyphosis (48 %), visual impairment (61 %) and hearing loss (38 %). Behavioral problems (86 %) and sleeping problems (64 %) also occurred frequently.</div></div><div><h3>Conclusion</h3><div>We report on the largest cohort of clinically studied individuals with ATR-X syndrome, including the eldest individuals, reported to date. Clinical knowledge is essential to improve care and to evaluate future therapies for this group.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105026"},"PeriodicalIF":1.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parental communication about inherited conditions with young Children: Insights from genetic professionals in Portugal 关于与幼儿遗传条件的父母沟通：来自葡萄牙遗传专业人士的见解。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-06-03 DOI: 10.1016/j.ejmg.2025.105025

Catarina Seidi , Liliana Sousa , Álvaro Mendes

{"title":"Parental communication about inherited conditions with young Children: Insights from genetic professionals in Portugal","authors":"Catarina Seidi , Liliana Sousa , Álvaro Mendes","doi":"10.1016/j.ejmg.2025.105025","DOIUrl":"10.1016/j.ejmg.2025.105025","url":null,"abstract":"<div><div>Genetic healthcare professionals (GHP) are key in supporting parents in communicating about inherited genetic conditions (IGC) with their young children. This study explored the attitudes, clinical practice and perceptions of Portuguese GHP’ regarding parental communication about IGC with young children. We conducted an observational and cross-sectional study with 32 GHP, 75 % of whom were women, and 37.5 % were aged 31–40 years old. The survey included sociodemographic and professional questions, along with 35 statements to be answered on a 4-point Likert scale (ranging from 1- strongly disagree to 4- strongly agree). Key findings show that GHP: (i) perceive that parents fear the impact of genetic information on their children's emotional wellbeing (3.53 ± 0.51), are receptive to support from GHP (3.16 ± 0.57), and should tailor communication to children's developmental stage (3.56 ± 0.50); (ii) report being available to support parents when asked (3.56 ± 0.62) and encourage parents to communicate openly (3.47 ± 0.57); and (iii) assess parents' level of understanding about the IGC (3.41 ± 0.56), raise parents' awareness of the importance of informing their children (3.28 ± 0.52), and support parents in adapting communication to the type of IGC (3.28 ± 0.58), and the child's developmental stage (3.22 ± 0.55). Results emphasize critical role of GHP in facilitating parent-child communication about IGC, highlighting their commitment to supporting these sensitive conversations.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105025"},"PeriodicalIF":1.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel STAG2 variant expands Mullegama-Klein-Martinez Syndrome phenotype 新的STAG2变异扩大了Mullegama-Klein-Martinez综合征的表型。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-31 DOI: 10.1016/j.ejmg.2025.105024

Cormac Duff , Samy Allawendy , Andrew J. Green , Michael Riordan , Eirin Carolan , Jacqueline McBrien

{"title":"Novel STAG2 variant expands Mullegama-Klein-Martinez Syndrome phenotype","authors":"Cormac Duff , Samy Allawendy , Andrew J. Green , Michael Riordan , Eirin Carolan , Jacqueline McBrien","doi":"10.1016/j.ejmg.2025.105024","DOIUrl":"10.1016/j.ejmg.2025.105024","url":null,"abstract":"<div><div><strong>We present a novel case of a female patient with a de novo heterozygous splice site pathogenic variant STAG2 (NM_001042749.3):c.1196 + 4_1196+7del.</strong> The <em>STAG2</em> gene encodes \"Stromal Antigen 2\" (STAG2), a fundamental subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Pathogenic STAG2 gene variants are associated with Mullegama-Klein-Martinez Syndrome (MKMS), a rare X-linked cohesinopathy. This patient exhibits symptoms not previously associated with MKMS, thereby expanding the known clinical phenotype of this rare disease. The patient has severe intellectual disability, microcephaly, short stature, and a single front tooth. She also has an ectopic posterior pituitary gland, resulting in vasopressin deficiency (formerly known as central diabetes insipidus), which was associated with adipsia, causing profound hypernatraemic dehydration and acute renal failure necessitating peritoneal dialysis. STAG2 pathogenic variants should prompt in-depth imaging of the pituitary fossa for pituitary malformations. Clinical and biochemical screening and surveillance should be performed to identify pituitary dysfunction.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105024"},"PeriodicalIF":1.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Partial 3q tetrasomy: Defining the syndrome, neocentromeres, and an additional case report 部分3q四体：定义综合征，新中心粒，和一个额外的病例报告。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-30 DOI: 10.1016/j.ejmg.2025.105021

Mads E. Hauberg , Aia E. Jønch , Christina R. Fagerberg

{"title":"Partial 3q tetrasomy: Defining the syndrome, neocentromeres, and an additional case report","authors":"Mads E. Hauberg , Aia E. Jønch , Christina R. Fagerberg","doi":"10.1016/j.ejmg.2025.105021","DOIUrl":"10.1016/j.ejmg.2025.105021","url":null,"abstract":"<div><div>Partial 3q tetrasomy is an ultra-rare genetic condition, with a phenotype that has hitherto not been comprehensively reviewed. In this paper we report the 18th case and re-evaluate those previously published.</div><div>The present case presented with dysmorphic features, malformations, cognitive deficits, end-stage renal disease, a surgically corrected tethered chord/scoliosis along with skin pigmentary changes and had remained without a diagnosis for 23 years. Blood and fibroblast karyotyping and exome sequencing yielded a normal result. Chromosomal microarray analysis on uncultured skin biopsies showed a mosaic amplification of the terminal 34 Mb of 3q. Subsequent fluorescence <em>in situ</em> hybridisation on cultured cells showed that a few metaphases contained a small supernumerary marker chromosome (sSMC) consisting of two head-to-head copies of the amplified 3q-material with neocentromere formation, the lower degree of mosaicism in karyotyping being ascribed to loss of sSMC upon culturing.</div><div>Reviewing the published cases of partial 3q tetrasomy cases we find pigmentary changes along the lines of Blaschko, cognitive deficits, spinal malformations, depressed nasal bridge, and palatal deformities to be frequent findings, and highlight a phenotypic overlap with partial 3q trisomy. Symptoms spanned from mild to severe, likely depending on both the size of the amplification and the degree of mosaicism.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105021"},"PeriodicalIF":1.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hexasomy of the 15q11q13 region: a detailed report and review of the literature 15q11q13区域的六体：详细报道和文献综述。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-27 DOI: 10.1016/j.ejmg.2025.105023

Charissa Y.Z. Chan , Emma K. Baker , David Francis , Kate Milner , David J. Amor

{"title":"Hexasomy of the 15q11q13 region: a detailed report and review of the literature","authors":"Charissa Y.Z. Chan , Emma K. Baker , David Francis , Kate Milner , David J. Amor","doi":"10.1016/j.ejmg.2025.105023","DOIUrl":"10.1016/j.ejmg.2025.105023","url":null,"abstract":"<div><div>Hexasomy of the Prader-Willi/Angelman Syndrome Critical Region (PWASCR; chromosome 15q11-q13) is very rare with only 13 patients being described to date. The region is known for its high susceptibility to genomic rearrangements, and extra copies within the region have been shown to be associated with distinct but variable clinical features of intellectual disability, epilepsy, global developmental delay amongst others. We present a 10-year-old girl with moderate to severe intellectual disability, cerebral palsy, seizures, autistic features and challenging behaviours. Her karyotype is 47,XX,+mar[25]/46,XX[5]. On chromosome analysis using G-banding, we identified a very large dicentric supernumerary marker chromosome 15q11-q13. Microarray analysis and metaphase fluorescence in-situ hybridisation using the SNRPN gene specific to 15q11.2-q13.3 region showed 87 % of cells containing 6 signals and 13 % of cells containing 2 signals. This represents mosaicism for a partial hexasomy of the long arm of chromosome 15q. We also reviewed and consolidated the literature of all reported patients with hexasomy of PWASCR, and found that amongst all 14 patients (including ours), despite some variation in phenotype, all patients had seizures, and the majority had intellectual disability and challenging behaviours.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105023"},"PeriodicalIF":1.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variable expressivity of a transmitted pathogenic KAT6B variant 一种传染性致病性KAT6B变异的可变表达性

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-27 DOI: 10.1016/j.ejmg.2025.105020

Ninna Bager Rasmussen , Pernille Axél Gregersen , Trine Østergaard Nielsen , Line Graven Lyngdorf , Christine Kroer Nielsen , Casper Kruse , Michael Bayat , Philippe M. Campeau , Anne Skakkebæk

{"title":"Variable expressivity of a transmitted pathogenic KAT6B variant","authors":"Ninna Bager Rasmussen , Pernille Axél Gregersen , Trine Østergaard Nielsen , Line Graven Lyngdorf , Christine Kroer Nielsen , Casper Kruse , Michael Bayat , Philippe M. Campeau , Anne Skakkebæk","doi":"10.1016/j.ejmg.2025.105020","DOIUrl":"10.1016/j.ejmg.2025.105020","url":null,"abstract":"<div><div>Pathogenic variants in <em>KAT6B</em> (Lysine acetyltransferase 6B) are associated with two clinically overlapping autosomal dominant disorders Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM <span><span>603736</span><svg><path></path></svg></span>), and Genitopatellar syndrome (GPS) (OMIM <span><span>606170</span><svg><path></path></svg></span>). More recently, the clinical spectrum of <em>KAT6B</em> disorders has expanded and <em>KAT6B</em> disorders have been suggested to consist of a spectrum of disorders with intermediate and overlapping clinical manifestations. Pathogenic variants in <em>KAT6B</em> mainly occur <em>de novo</em>, with only 3 reports of inherited variants. Here, we describe clinical and molecular findings in a three-generation Danish family with a segregating, previously unreported, pathogenic <em>KAT6B</em> variant. The variant is associated with a phenotype not otherwise specified (neither SBBYSS nor GPS) and with variable expressivity, adding further evidence that <em>KAT6B</em> disorders should be seen as a broad clinical spectrum. Furthermore, we highlight the existence of intra-familial variability and that pathogenic variants in <em>KAT6B</em> can be inherited from mildly affected parents.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"76 ","pages":"Article 105020"},"PeriodicalIF":1.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wolcott-Rallison syndrome – crosstalk between PERK- EIF2A and type II interferon signaling Wolcott-Rallison综合征- PERK- EIF2A与II型干扰素信号之间的串扰。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-27 DOI: 10.1016/j.ejmg.2025.105022

Megha Konduri , Devin Boe , Nada Yazigi , Khalid Khan , Brant R. Ward , Blachy Davila Saldana , Douglas Cavener , Bhaskar Kallakury , Alexander Kroemer , Cal Matsumoto , Thomas Fishbein , Udeme D. Ekong

引用次数: 0

RHOA-associated disorder can be non-mosaic rhoa相关疾病可以是非镶嵌性的。

IF 1.6 4区医学

European journal of medical genetics Pub Date : 2025-05-23 DOI: 10.1016/j.ejmg.2025.105019

Daisuke Nakato , Naoya Morisada , Sota Iwatani , Chikako Nishida , Daisuke Watanabe , Mamiko Yamada , Hisato Suzuki , Fuyuki Miya , Kenjiro Kosaki , Toshiki Takenouchi

{"title":"RHOA-associated disorder can be non-mosaic","authors":"Daisuke Nakato , Naoya Morisada , Sota Iwatani , Chikako Nishida , Daisuke Watanabe , Mamiko Yamada , Hisato Suzuki , Fuyuki Miya , Kenjiro Kosaki , Toshiki Takenouchi","doi":"10.1016/j.ejmg.2025.105019","DOIUrl":"10.1016/j.ejmg.2025.105019","url":null,"abstract":"<div><div>Recurrent somatic mosaic pathogenic variants of <em>RHOA</em> have been observed in a newly identified neuroectodermal syndrome, Ectodermal Dysplasia with Facial Dysmorphism and Acral, Ocular, and Brain Anomalies, Somatic Mosaic [EDFAOB]. All 12 previously reported patients had somatic mosaicism for <em>RHOA</em> variants. Conversely, no patients with non-mosaic germline variants of <em>RHOA</em> have been reported. The absence of non-mosaic patients has been explained by the presumed lethal effect of all <em>RHOA</em> variants in non-mosaic status. Here we report an 11-month-old female with EDFAOB-like features but without Blaschko's skin lesions or asymmetry. Characteristic features included hypertelorism, 2–3 toes cutaneous syndactyly, cleft palate and duplicated uterus and kidney malformations. She carried the non-mosaic <em>de novo</em> germline variant <em>RHOA</em>:c.202C>A,p.(Arg68Ser) near the hotspot in the switch II region in peripheral blood and buccal swabs. The documentation of a living patient with a non-mosaic germline variant of <em>RHOA</em> negates the previous notion that patients with <em>RHOA</em> variants are not viable. The differential diagnosis of a “non-mosaic” RHOA-related disorder would include Ectodermal Dysplasia-Ectrodactyly-Clefting syndrome, as both conditions share ectodermal dysplasia, finger anomalies, and clefting. This phenotypic similarity may be explained by the known molecular interaction between TP63, the gene responsible for EEC syndrome, and RHOA. RHOA is a member of the RAC subfamily of small Rho family guanosine triphosphatases, which include RHOA, RAC1, RAC3, and CDC42 (Takenouchi-Kosaki syndrome). The documentation of germline RHOA-associated intellectual disability in the present article establishes that variants in all three genes of the RAC subfamily of small Rho family GTPases are associated with neurodevelopmental disorders.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"75 ","pages":"Article 105019"},"PeriodicalIF":1.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0