欧洲医学遗传学杂志 (EJMG) 是一份同行评审期刊，以英文发表关于人类和医学遗传学以及实验模型遗传学的各个方面的文章。原创临床和实验研究文章、简短的临床报告、评论文章和欢迎就以下主题给编辑写信：• 畸形学和综合征描述• 遗传性疾病的分子遗传学和分子细胞遗传学• 基因组学和下一代测序技术的临床应用• 综合征癌症遗传学• 行为遗传学• 社区遗传学• 胎儿病理学和产前诊断• 遗传咨询。

The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles on various aspects of human and medical genetics, as well as experimental model genetics. We welcome original clinical and experimental research articles, brief clinical reports, and review articles. The journal particularly focuses on the following topics: • Morphology and syndrome descriptions • Molecular genetics and molecular cytogenetics of hereditary diseases • Clinical applications of genomics and next-generation sequencing technologies • Genetic aspects of syndromic cancers • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.

《欧洲医学遗传学杂志》(European Journal of Medical Genetics) 是一本经过同行评审的期刊，主要发表关于人类医学遗传学及实验模型遗传学各个方面的研究文章。我们欢迎原创的临床和实验研究、简短的临床报告以及评论文章。期刊特别关注以下主题：• 畸形学与综合征描述 • 遗传性疾病的分子遗传学与分子细胞遗传学 • 基因组学及下一代测序技术的临床应用 • 综合征癌症遗传学 • 行为遗传学 • 社区遗传学 • 胎儿病理学与产前诊断 • 遗传咨询。

European Journal of Medical Genetics

Cardiovascular diseases are the most common cause of death globally. In which atrioventricular block (AVB) is a common disorder with genetic causes, but the responsible genes have not been fully identified yet. To determine the underlying causative genes involved in cardiac AVB, here we report a three-generation Chinese family with severe autosomal dominant cardiac AVB that has been ruled out as being caused by known genes mutations.

Guohui Liu

Ziying Yang

Weiwei Chen

Junguang Xu

Liangwei Mao

Qinlin Yu

Jian Guo

Hui Xu

Fengxia Liu

Yan Sun

Hui Huang

Zhiyu Peng

Jun Sun

Wei Li

Ping Yang

European journal of medical genetics

Eur J Med Genet

Novel missense variant in TTN cosegregating with familial atrioventricular block.

Arthrogryposis has been the term used to describe multiple congenital contractures for over a century. It is a descriptive term and present in over 400 specific conditions. Responsible gene abnormalities have been found for more than 150 specific types of arthrogryposis. Decreased fetal movement is present in all affected individuals which leads to a variety of secondary deformations. Decreased fetal movement (fetal akinesia) is associated with increased connective tissue around the immobilized joint, skin dimpling overlying the immobilized joint, disuse atrophy of the muscles that mobilize the joint and abnormal surface of the joint depending on the immobilized position. Other frequently observed features include: micrognathia, mildly shortened limbs, intrauterine growth restriction, pulmonary hypoplasia and short and/or immature gut. Primary etiologies include neuropathic processes; myopathic processes; end-plate abnormalities; maternal illness, trauma and drugs; limitation of fetal space; vascular compromise; and metabolic disorders to the developing embryo/fetus.

Judith G Hall

Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.

Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12-related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, important speech delay, behavior problems, dysmorphic facial features and hearing loss. NGS allows us to detect the MED12 missense variant c.3883C > T (p.(Arg1295Cys)) carried by the three patients. This variant has been reported in 2016 by Hu et al. in one family from a big cohort of XLID families. This clinical report contributes to expanding the phenotype associated with MED12-mutations.

Elisa Rubinato

Sophie Rondeau

Fabienne Giuliano

Manoelle Kossorotoff

Marine Parodi

Souad Gherbi

Julie Steffan

Laurence Jonard

Sandrine Marlin

MED12 missense mutation in a three-generation family. Clinical characterization of MED12-related disorders and literature review

Aging is a physiological process that is in part genetically determined. Some of the signs and symptoms of aging also occur prematurely in Mendelian disorders. Such disorders are excellent sources of information of underlying mechanisms for these components of aging, and studying these may allow detection of pathways that have not yet considered in detail in physiological aging. Here I define the clinical characteristics that constitute aging and propose that at least 40% of aging signs and symptoms should be present before an entity should be tagged as progeroid. A literature search using these characteristics yields 17 entities that fulfill this definition: Hutchinson-Gilford progeria, mandibulo-acral dysplasia, Nestor-Guillermo progeria, Werner syndrome, Cockayne syndrome, cutis laxa progeroid, Penttinen progeroid syndrome, Mandibular underdevelopment, Deafness, Progeroid features, Lipodystrophy, Fontaine progeroid syndrome, SHORT syndrome, Wiedemann-Rautenstrauch syndrome, Mulvihill-Smith syndrome, dyskeratosis congenita, Marfan syndrome lipodystrophy type, Warburg-Cinotti syndrome, Lessel syndrome and Bloom syndrome. The presenting and main characteristics of these entities are indicated briefly. Their pathophysiology is not complete pathophysiology is reviewed but only the pathophysiology of the premature aging characteristics of this series of entities is compared to the known mechanisms ("Hallmarks") of physiological aging as summarized in the review paper by Lopez-Otin and colleagues. Although many causative genes have not been studied fully for all known aging mechanisms the comparison demonstrates that additional mechanisms must play a role to explain the aging characteristic in some of the progeroid entities of the progeroid entities, and possibly also in physiological aging.

Raoul C.M. Hennekam

Pathophysiology of premature aging characteristics in Mendelian progeroid disorders

孟德尔早衰症候群早衰特征的病理生理学

Shprintzen-Goldberg syndrome is a rare systemic connective tissue disorder caused by heterozygous mutations in the Sloan-Kettering Institute (SKI) gene. The clinical presentation is reminiscent of Marfan and Loeys-Dietz syndromes, making differential diagnosis challenging. Shprintzen-Goldberg syndrome's distinctive features are craniosynostosis and learning disabilities. The pathophysiology of these three conditions is similar as they all result in the deregulation of the transforming growth factor beta (TGF-β) signaling pathway and thus an altered expression of TGF-β responsive genes. We report a family of two patients: one with initial suspicion of hypermobile Ehlers-Danlos syndrome and the second with suspicion of Marfan syndrome, as the Marfan systemic score was positive and no craniosynostosis or learning disabilities were described. They were diagnosed with Shprintzen-Goldberg syndrome after a heterozygous probably pathogenic variant in the second mutational hotspot of SKI Dachshund homology domain was identified. We reviewed the genotype-phenotype correlation among the three mutational hotspots in SKI: the amino acids 20 to 35 of the receptor-regulated small mothers against decapentaplegic domain (group 1, n=32), amino acids 94 to 117 of Dachshund homology domain (group 2, n=12), and threonine 180 of Dachshund homology domain (group 3, n=11 including our patients). As the main differential diagnoses of Shprintzen-Goldberg syndrome are Marfan and Loeys-Dietz syndromes, we completed the comparison already made by Loeys et al. (2018) of Shprintzen-Goldberg syndrome clinical features among the different mutational hotspots with Marfan syndrome and the different types of Loeys-Dietz syndrome. In addition to the already described absence of learning disabilities in Shprintzen-Goldberg patients with a pathogenic variant in the threonine 180 of Dachshund homology domain, facial features also appeared to be less severe. The clinical overlap with Marfan and Loeys-Dietz patients requires genetic testing in order to establish an accurate molecular diagnosis at the variant level, and to adapt genetic counseling and clinical management.

Camille Chatelain

Léna Kukor

Sophie Bailleux

Vincent Bours

Saskia Bulk

Elisa Docampo

Shprintzen – Goldberg syndrome without intellectual disability: a clinical report and review of literature

无智力障碍的Shprintzen-Goldberg综合征：临床报告与文献综述

Biallelic loss-of-function variants in STRC contribute to mild-moderate hearing loss (DFNB16). Here, we report a female patient with mild hearing loss. Exome sequencing and MLPA analysis revealed STRC biallelic inactivation due to a nonsense and a CKMT1B-STRC deletion. Analysis of the self-reported normal-hearing parents revealed inconsistent mendelian inheritance. Indeed, the mother was a heterozygous carrier of a CKTM1B-STRC-CATSPER2 deletion, and the father shared the same genotype as his daughter. He was later found to also have mild-moderate hearing loss. To address these discrepancies, we used long-read sequencing and optical genome mapping. We demonstrated that the father, in fact, carried a CKMT1B-STRC-CATSPER2 deletion in trans with the STRC nonsense variant and a tandem duplication of CATSPER2-CKMT1A. The proband inherited this latter haplotype, together with the maternal CKMT1B-STRC-CATSPER2 deletion. Combining these two technologies allowed us to fully elucidate the complex structural rearrangements at the STRC locus and provide appropriate genetic counselling.

Sacha Laurent

Anne Vannier

Corinne Gehrig

Marc Abramowicz

Ariane Paoloni-Giacobino

Hélène Cao Van

Michel Guipponi

Improved variant detection using long-read sequencing and optical mapping : illustration in STRC-related hearing loss

使用长读长测序和光学图谱提高变异检测：以STRC相关听力损失为例

Achondroplasia is a common skeletal dysplasia caused by a mutation in the FGFR3 gene, leading to disproportionate short stature and various clinical features. Despite the absence of definitive pharmacological treatments, mindfulness-based interventions may offer psychosocial benefits for affected individuals and their families.

Àngel Casellas

Anna Casellas-Grau

Àngel Serra

Ester Busquets-Alibés

Feasibility study of the psychosocial effects of an online mindfulness intervention in children and adolescents with achondroplasia and their parents

在线正念干预对软骨发育不全儿童和青少年及其父母心理社会影响的可行性研究

Nonsense-mediated mRNA decay represents a biologic clearing system against aberrant mRNAs harboring nonsense and frameshift mutations and depends on three factors, UPF1, UPF2, and UPF3 (UPF3A, UPF3B). While germline pathogenic variants of UPF3B and UPF2 are known to be associated with neurodevelopmental disorders, germline variants in UPF1 have not been reported, until date, as being associated with any human disorders. Herein, we report two unrelated patients with de novo UPF1 variants. Patient 1 was a 5-year-old girl with intellectual disabilities, frontal bossing, hypertelorism, high frontal hairline, and thin upper lip. Patient 2 was a 2-year-old female child with intellectual disabilities and similar features. Trio exome analysis revealed a de novo heterozygous variant in UPF1 in both the patients (Patient 1: NM_002911.4): c.949_951del, p. (Asp317del); Patient 2: c.1984G>A, p. (Asp662Asn)). We conducted experiments using Drosophila models to evaluate the functional relevance of these UPF1 variants. Enforced expression of the wild-type Upf1 allele under the control of the pan-neuronal nSyb-GAL4 driver caused mortality, mostly at the pupal stage, but still yielded adult flies. By contrast, expression of the Asp294del (Asp317del in humans) variant caused embryonic or early larval lethality and that of the Asp643Asn (Asp662Asn in humans) caused third instar larval lethality; neither produced pupa nor adult fly. Thus, the developmental defects caused by the variants, especially Asp294del, were more severe than those caused by the wild-type allele. These observations suggest that both variants are deleterious mutations. In conclusion, germline variants in UPF1 are associated with intellectual disabilities in humans.

Daisuke Nakato

Yuri Yasue

Kohei Matsubara

Hisato Suzuki

Rika Kosaki

Toshiki Takenouchi

Mamiko Yamada

Fuyuki Miya

Toshiyuki Takano-Shimizu

Kenjiro Kosaki

De novo variants in UPF1 associated with intellectual disabilities: Human genetic and functional evidences using Drosophila model

UPF1相关新生变异与智力障碍：利用果蝇模型的人类遗传和功能证据

Hypohidrotic Ectodermal Dysplasia is a syndrome with hypotrichosis, hypohidrosis, and hypodontia as the main symptoms. The prevalence is estimated to one in 5,000-10,000 persons. In 10-15% the disease is caused by pathogenic variants in EDAR, and most of the known causal variants to date are missense or nonsense variants. We present af patient with classic Hypohidrotic Ectodermal Dysplasia and mammary gland aplasia with a duplication within EDAR as the likely cause. The duplication is de novo in the patient, and genome sequencing of DNA extracted from blood has revealed that the duplication is in tandem conformation, most likely entailing an altered EDAR protein with a dominant negative effect. This is to our knowledge the first report of an intragenic duplication in EDAR as causal for Hypohidrotic Ectodermal Dysplasia.

Abbreviation	Eur. J. Med. Genet.
Journal Impact	1.43
Quartiles(Global)	GENETICS & HEREDITY(Q3)

ISSN	1769-7212, 1878-0849
h-index	64

Publication Information	Publisher: Elsevier Masson s.r.l.，Publishing cycle: Quarterly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2005，Proportion of original research papers: 86.47%，Self Citation Rate:0.00%， Gold OA Rate: 29.31%
Average review cycle	网友分享经验：偏慢,4-8周
Average recruitment ratio	网友分享经验：容易

European Journal of Medical Genetics

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Novel missense variant in TTN cosegregating with familial atrioventricular block.

Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles.

MED12 missense mutation in a three-generation family. Clinical characterization of MED12-related disorders and literature review

Pathophysiology of premature aging characteristics in Mendelian progeroid disorders

Shprintzen – Goldberg syndrome without intellectual disability: a clinical report and review of literature

Shprintzen – Goldberg syndrome without intellectual disability: a clinical report and review of literature

Improved variant detection using long-read sequencing and optical mapping : illustration in STRC-related hearing loss

Feasibility study of the psychosocial effects of an online mindfulness intervention in children and adolescents with achondroplasia and their parents

De novo variants in UPF1 associated with intellectual disabilities: Human genetic and functional evidences using Drosophila model

Hypohidrotic Ectodermal Dysplasia caused by an intragenic duplication in EDAR