Journals European Journal of Medical Ge...

European Journal of Medical Genetics
Thomas Funck-Brentano, M Carola Zillikens, Gavin Clunie, Heide Siggelkow, Natasha M Appelman-Dijkstra, Martine Cohen-Solal
Osteopetrosis refers to a group of related rare bone diseases characterized by a high bone mass due to impaired bone resorption by osteoclasts. Despite the high bone mass, skeletal strength is compromised and the risk of fracture is high, particularly in the long bones. Osteopetrosis was classically categorized by inheritance pattern into autosomal recessive forms (ARO), which are severe and diagnosed within the first years of life, an intermediate form and an autosomal dominant (ADO) form; the latter with variable clinical severity and typically diagnosed during adolescence or in young adulthood...
April 7, 2024: European Journal of Medical Genetics
David A Pearce
Individual researchers and consortia have been studying rare diseases for several decades. However, the rare disease community can be very fragmented mainly due to the large heterogeneity of rare diseases. Indeed, for many diseases, there is a very limited amount of researchers and resources available. Concerted efforts to organize the rare disease community and funding were emerging in several countries but so far, international coordination was rather limited. The International Rare Diseases Research Consortium (IRDiRC) aims to correct this...
April 5, 2024: European Journal of Medical Genetics
Ieva Tevelyte, Paulius Bertasius, Kristina Aleknaviciene, Rimvydas Jonikas, Justina Klimaite, Edita Jasinskiene, Rasa Traberg
Hajdu-Cheney syndrome (HCS) is an extremely rare autosomal dominant skeletal disorder. The prevalence rate of less than 1 case per 1,000,000 newborns and only 50 cases were reported in the medical literature. HCS is characterized by progressive bone resorption in the distal phalanges (acro-osteolysis), progressive osteoporosis, distinct craniofacial changes, dental anomalies, and occasional association with renal abnormalities. HCS is caused by pathogenic variants in the NOTCH2 gene, 34th exon. We report first familial case of HCS caused by likely pathogenic variant of NOTCH2 gene c...
April 3, 2024: European Journal of Medical Genetics
Laura Krogh Herlin, Morten Krogh Herlin, Jenny Blechingberg, Kirsten Marthine Rønholt Stausholm, Lise Graversen, Sigrún Alba Jóhannesdóttir Schmidt, Mette Warming Jørgensen, Michel Bach Hellfritzsch, Jannie Dahl Hald, Signe Sparre Beck-Nielsen, Hans Gjørup, Brian Nauheimer Andersen, Pernille Axél Gregersen, Mette Sommerlund
Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years...
April 2, 2024: European Journal of Medical Genetics
Natalie Ciantar, Graziella Zahra, Julian Delicata, Fiona Sammut, Jean Calleja-Agius, Emanuel Farrugia, Edith Said
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features. METHODS: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS)...
March 25, 2024: European Journal of Medical Genetics
Servane de Masfrand, Benjamin Cogné, Mathilde Nizon, Wallid Deb, Alice Goldenberg, François Lecoquierre, Gaël Nicolas, Marie Bournez, Antonio Vitobello, Frédéric Tran Mau-Them, Gwenaël le Guyader, Frédéric Bilan, Peter Bauer, Christiane Zweier, Juliette Piard, Laurent Pasquier, Stéphane Bézieau, Bénédicte Gerard, Laurence Faivre, Pascale Saugier-Veber, Amélie Piton, Bertrand Isidor
PURPOSE: Incomplete penetrance is observed for most monogenic diseases. However, for neurodevelopmental disorders, the interpretation of single and multi-nucleotide variants (SNV/MNVs) is usually based on the paradigm of complete penetrance. METHOD: From 2020 to 2022, we proposed a collaboration study with the French molecular diagnosis for intellectual disability network. The aim was to recruit families for whom the index case, diagnosed with a neurodevelopmental disorder, was carrying a pathogenic or likely pathogenic variant for an OMIM morbid gene and inherited from an asymptomatic parent...
March 5, 2024: European Journal of Medical Genetics
Claudia Azuelos, Marc-Antoine Marquis, Anne-Marie Laberge
PURPOSE: Exome sequencing (ES) and genome sequencing (GS) are diagnostic tests for rare genetic diseases. Studies report clinical utility of ES/GS. The goal of this systematic review is to establish how clinical utility is defined and measured in studies evaluating the impacts of ES/GS results for pediatric patients. METHODS: Relevant articles were identified in PubMed, Medline, Embase, and Web of Science. Eligible studies assessed clinical utility of ES/GS for pediatric patients published before 2021...
March 1, 2024: European Journal of Medical Genetics
Álvaro Mendes, Milena Paneque, Jorge Sequeiros
This paper presents the perspectives of healthcare professionals regarding their roles and responsibilities in supporting patients with the disclosure of genetic risk to their families. The study involved eight focus groups and two individual interviews with 34 healthcare professionals working in medical genetics services across Portugal. The data were analyzed thematically, resulting in three primary themes: i) informing patients about the risk to relatives; ii) ensuring patient confidentiality; and iii) encouraging family communication...
February 29, 2024: European Journal of Medical Genetics
Somayeh Khoddam, Neda Kamal, Amirmasoud Shiri, Hossein Jafari Khamirani, Jamal Manoochehri, Mehdi Dianatpour, Seyed Mohammad Bagher Tabei, Seyed Alireza Dastgheib
The PEX11β gene contains four exons and encodes peroxisomal membrane protein 11β, which is involved in peroxisome proliferation and division. Pathogenic variants in this gene result in a rare genetic disorder with autosomal recessive inheritance called peroxisome biogenesis disorder 14B (MIM: 614920). Here, we report two affected siblings with a novel variant (NM_003846: c.11G > A, p. Trp4Ter) in the PEX11β gene that was identified by whole exome sequencing and confirmed by Sanger sequencing...
February 27, 2024: European Journal of Medical Genetics
Surya Balakrishnan, Iravathy Goud, Madhavi Latha Teegala
GAPO syndrome is a rare genetic condition caused by bi-allelic variants in ANTXR1 gene & is an abbreviation for its core features - growth retardation, alopecia, pseudo-anodontia & optic atrophy. Certain additional features involving various other systems have been reported over the years & contribute to the expanding spectrum of this evolving phenotype. We report GAPO syndrome in a 3.75 year old Indian female child, who presented with some unique features such as sagittal craniosynostosis with scaphocephaly & bilateral choroid plexus cysts, alongside the core phenotype...
February 27, 2024: European Journal of Medical Genetics
Engin Köse, Çiğdem Seher Kasapkara, Aslı İnci, Yılmaz Yıldız, İlknur Sürücü Kara, Ayça Burcu Kahraman, Leyla Tümer, Ali Dursun, Fatma Tuba Eminoğlu
BACKGROUND: Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the MAN2B1 gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly. This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics...
February 19, 2024: European Journal of Medical Genetics
Silvia Gazzotti, Rebecca Sassi, Maria Pilar Aparisi Gómez, Alice Moroni, Evelise Brizola, Marco Miceli, Alberto Bazzocchi
Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging...
February 16, 2024: European Journal of Medical Genetics
Tuğba Daşar, Adalet Elçin Yıldız, Gökhan Demirkıran, Gülen Eda Utine, Pelin Özlem Şimşek Kiper
Diaphanospondylodysostosis is a rare genetic skeletal disorder caused by biallelic variants in the BMPER gene. The term, diaphanospondylodysostosis, includes ischiospinal dysotosis, which was previously known as a distinct entity with milder clinical features. The clinical phenotype of diaphanospondylodysostosis is quite variable with mortality in early postnatal life in some patients. Main clinical and radiographic features are narrow thorax, vertebral segmentation defects, rib anomalies, ossification defects of vertebrae, ischium and sacrum, and renal cysts...
February 12, 2024: European Journal of Medical Genetics
M Tusseau, M Eyries, N Chatron, F Coulet, A Guichet, E Colin, B Demeer, H Maillard, J Thevenon, C Lavigne, V Saillour, C Paris, J M De Sainte Agathe, M Pujalte, A Guilhem, S Dupuis-Girod, G Lesca
Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is a dominant inherited vascular disorder. The clinical diagnosis is based on the Curaçao criteria and pathogenic variants in the ENG and ACVRL1 genes are responsible for most cases of HHT. Four families with a negative targeted gene panel and selected by a multidisciplinary team were selected and whole-genome sequencing was performed according to the recommendations of the French National Plan for Genomic Medicine. Structural variations were confirmed by standard molecular cytogenetic analysis (FISH)...
February 12, 2024: European Journal of Medical Genetics
Lottie D Morison, Olivia Van Reyk, Emma Baker, Lyse Ruaud, Nathalie Couque, Alain Verloes, David J Amor, Angela T Morgan
Pathogenic variants in BRPF1 cause intellectual disability, ptosis and facial dysmorphism. Speech and language deficits have been identified as a manifestation of BRPF1-related disorder but have not been systematically characterized. We provide a comprehensive delineation of speech and language abilities in BRPF1-related disorder and expand the phenotype. Speech and language, and health and medical history were assessed in 15 participants (male = 10, median age = 7 years 4 months) with 14 BRPF1 variants...
February 10, 2024: European Journal of Medical Genetics
Anne Kathrine Møller Nielsen, Anna Maria Dehn, Vibeke Hjortdal, Lars Allan Larsen
T-Box Transcription Factor 5 (TBX5) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between TBX5 variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants in TBX5 associated with a cardiac phenotype in 277 patients. Arrhythmias were more frequent in patients with a missense variant (48% vs 30%, p = 0...
February 7, 2024: European Journal of Medical Genetics
Zografia Zervou, Roel Plooij, Evert F S van Velsen, Remco G M Timmermans, Serwet Demirdas, M Carola Zillikens
Hypophosphatasia (HPP) is a rare disorder, resulting from loss-of-function variants of the ALPL gene encoding non-tissue specific alkaline phosphatase (TNSALP). Presentation varies largely, with increased severity usually occurring with earlier disease onset. Here we describe the clinical improvement of a 57-year-old woman with childhood onset HPP, after initiating treatment with asfotase alfa (Strensiq®). This was started because of the rapid and progressive radiological deterioration of bone structure after placement of nails in both upper legs for spontaneous atypical femur fracture (AFF) - like fractures...
February 5, 2024: European Journal of Medical Genetics
Yu Jiang, Zhenyu Luo, Wenrong Wang, Xingxiu Lu, ZhongMin Xia, Jieqiong Xie, Mei Lu, Lili Wu, Yulin Zhou, Qiwei Guo
Heterozygous carriers of the survival of motor neuron 1 (SMN1) gene deletion in parents account for approximately 95% of neonatal spinal muscular atrophy cases. Given the severity of the disease, professional organizations have recommended periconceptional spinal muscular atrophy carrier screening to all couples, regardless of race or ethnicity. However, the prevalence of screening activities in mainland China remains suboptimal, mainly attributed to the limitations of the existing carrier screening methods...
February 5, 2024: European Journal of Medical Genetics
Kelley L Colvin, Kristine Wolter-Warmerdam, Francis Hickey, Michael E Yeager
OBJECTIVES: We tested the hypothesis that aberrant expression of Hsa21-encoded interferon genes in peripheral blood immune cells would correlate to immune cell dysfunction in children with Down syndrome (DS). STUDY DESIGN: We performed flow cytometry to quantify peripheral blood leukocyte subtypes and measured their ability to migrate and phagocytose. In matched samples, we measured gene expression levels for constituents of interferon signaling pathways. We screened 49 children, of which 29 were individuals with DS...
February 5, 2024: European Journal of Medical Genetics
Clair Habib, Tamar Paperna, Rinat Zaid, Sarit Ravid, Josef Ben Ari, Galit Tal, Karin Weiss, Tova Hershkovitz
Increasingly, next-generation sequencing (NGS) is becoming an invaluable tool in the diagnosis of unexplained acute neurological disorders, such as acute encephalopathy/encephalitis. Here, we describe a brief series of pediatric patients who presented at the pediatric intensive care unit with severe acute encephalopathy, initially suspected as infectious or inflammatory but subsequently diagnosed with a monogenic disorder. Rapid exome sequencing was performed during the initial hospitalization of three unrelated patients, and results were delivered within 7-21 days...
February 5, 2024: European Journal of Medical Genetics
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