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Junfu Luo Wenwen Zhang Qingfu Zeng Weimin Zhou Qing Cao Wei Zhou 《European journal of medical genetics》2018,61(2):68-71
Deep venous thrombosis (DVT) remains a serious clinical problem that affects millions of people worldwide. Some DVT cases are caused by inherited thrombophilia derived from genetic aberrations and several disease-causing genes have been identified so far. Among them, HRG is an uncommon one with limited related reports. Here, we reported on a family with early-onset DVT where acquired risky conditions were excluded. Whole exome sequencing revealed a novel heterozygous single base pair substitution in exon 2 of HRG gene resulting in a conserved residue replacement of the protein (c. C271T, p. P73S). Sanger sequencing confirmed the co-segregation of the mutation and plasma quantification determined circulating protein deficiency. The mutation might therefore impair hemostatic balance by causing reduced circulating HRG level. Our study broadens the mutation spectrum of the HRG gene and underscores the importance of its function in regulating coagulation pathway. 相似文献
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Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B 下载免费PDF全文
Christeen Ramane J. Pedurupillay Tuva Barøy Asbjørn Holmgren Anne Blomhoff Magnus D. Vigeland Ying Sheng Eirik Frengen Petter Strømme Doriana Misceo 《American journal of medical genetics. Part A》2015,167(3):657-663
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《European journal of medical genetics》2020,63(4):103849
The bric-a-brac, tramtrack and broad complex (BTB) superfamily of conserved proteins are involved in ubiquitin-proteasome system that contains the Kelch-like (KLHL) gene family. Kelch-like family member 7 (KLHL7), one of the KLHL gene family, consists of one BTB/POZ domain, one BACK domain and five or six Kelch motifs. Numerous variants in KLHL7 gene domains have been reported with Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like features and retinitis pigmentosa 42, and have recently been identified as causing Bohring-Opitz syndrome (BOS)-like features. We report two siblings with BOS-like phenotype with healthy parents and living in Qazvin province (Central Iran).We performed whole-exome sequencing (WES) on the older patient and Sanger sequencing was carried out for validation of potential causative variants in the close family.A novel homozygous frameshift mutation, p.(Phe83Leufs*3), was identified in the BTB domain of KLHL7 that caused a premature translation-termination codon (PTC) in the two siblings with severe developmental delay, microcephaly, facial dysmorphism, peripheral retinal and optic disc atrophy and cardiac septal defects.Our findings are in agreement with the clinical spectrum of KLHL7 mutations, which are associated with BOS-like features that reports for first time in our population. 相似文献
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《European journal of medical genetics》2022,65(11):104608
Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP. Herein, we report the case of the first Chinese SPG62 patient, explore the potential pathogenic mechanism and review ERLIN1-related HSP patients. A 23-year-old man had progressive difficulty in walking and gait abnormalities for more than 11 years. Physical examination showed slightly reduced muscle strength (5-/5) and elevated muscle tone in the lower limbs and hyperreflexia in four limbs. Genetic analysis identified a novel splicing site mutation in ERLIN1 gene (c.504+1G > A), which was predicted to disturb the normal splicing process of mRNA by bioinformatic tools. Minigene experiment further confirmed the mutation c.504+1G > A could cause erroneous deletion of Exon 7 in the mRNA, which may change the conserved prohibitin (PHB) domain of erlin-1 and affect the function of erlin1/2 complex. Thus, we identified a pathogenic mutation of ERLIN1 splicing site causing delayed-onset pure HSP. This study widened the genetic and phenotypic spectrum of SPG62. 相似文献
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《European journal of medical genetics》2017,60(10):559-564
Methyl-CpG-binding domain 5 (MBD5)-associated neurodevelopmental disorder caused by 2q23.1 or MBD5-specific mutation has been recently identified as a genetic disorder associated with autism spectrum disorders. Phenotypic features of 2q23.1 deletion or disruption of MBD5 gene include severe intellectual disability, seizure, significant speech impairment, sleep disturbance, and autistic-like behavioural problems. Here we report a 7-year-old girl with intellectual disability and epilepsy without previous clinical diagnosis. Diagnostic exome sequencing identified a novel frameshift mutation c.254_255delGA (p.Arg85Asnfs*6) in the MBD5 gene of the proband and her father. The proband's father with normal intelligence showed subclinical manifestations observed in subsequent investigations. Clinical manifestations, disease course, and molecular findings of the involvement of MBD5 gene in this family suggest an unusual MBD5-related neurodevelopmental disorder. Moreover, this report demonstrates the critical role of next-generation sequencing technique in characterizing such a rare disorder with variable or no clinical manifestation and providing opportunity to develop effective preventive measures such as pre-implantation genetic diagnosis. 相似文献
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目的:对1例不明原因生长发育过快及心脏畸形的患儿进行临床表型及遗传学病因分析。方法:对先证者进行全外显子测序分析,应用Sanger测序技术对全外显子筛出的可疑致病基因的变异位点进行验证,并利用生物信息学软件进行功能预测分析。结果:全外显子测序结果显示,先证者在
FBN1基因的第48外显子上存在c.5846_... 相似文献
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Giordano L Sartori S Russo S Accorsi P Galli J Tiberti A Bettella E Marchi M Vignoli A Darra F Murgia A Bernardina BD 《American journal of medical genetics. Part A》2010,(12):3133-3137
Recently, it has been reported that longer expansions of the polyalanine tract of the ARX gene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARX gene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARX is involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations. 相似文献
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Lucie Sedláčková Petra Laššuthová Katalin Štěrbová Markéta Vlčková Martin Kudr Irena Buksakowska David Staněk Pavel Seeman 《European journal of medical genetics》2021,64(9):104263
IntroductionBiallelic variants in the SLC1A4 gene have been so far identified as a very rare cause of neurodevelopmental disorders with or without epilepsy and almost exclusively described in the Ashkenazi-Jewish population.Patients and methodsHere we present Czech patient with microcephaly, severe global developmental delay and intractable seizures whose condition remained undiagnosed despite access to clinical experience and standard diagnostic methods including examination with an epilepsy targeted NGS gene panel.ResultsWhole exome sequencing revealed a novel variant NM_003038.4:c.1370G > A p.(Arg457Gln) of the SLC1A4 gene in a homozygous state in the patient, and afterwards Sanger sequencing in both parents confirmed the biallelic origin of the variant. A variant in the same codon, but with a different amino acid exchange, was described previously in a patient that had a very similar phenotype, however, without epilepsy.ConclusionOur data suggest that the SLC1A4 gene should be considered in the diagnosis of patients with severe, early onset neurodevelopmental impairment with epilepsy and encourage the analysis of SLC1A4 gene variants via targeted NGS gene panel or whole exome sequencing. 相似文献
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We have recently performed exome analysis in a 7 year boy who presented in infancy with an encephalopathy characterized by ataxia and myoclonic epilepsy. Parents were not consanguineous and there was no family history of the disease. Exome analysis did not show any pathogenic variants in genes known to be associated with seizures and/or ataxia in children, including all known human channelopathies. However, we have identified a mutation in KCNA2 that we believe to be responsible for the disease in our patient. This gene, which encodes a member of the potassium channel, voltage‐gated, shaker‐related subfamily, has not been previously described as a cause of disease in humans, but mutations of the orthologous gene in mice (Kcna2) are known to cause both ataxia and convulsions. The mutation is c.890C>A, leading to the amino acid substitution p.Arg297Gln, which involves the second of the critical arginines in the S4 voltage sensor. This mutation is characterized as pathogenic by five different prediction programs. RFLP analysis and Sanger sequencing confirmed the presence of the mutation in the patient, but not in his parents, characterizing it as de novo. We believe that this discovery characterizes a new channelopathy. 相似文献
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Bernstein JA Bernstein D Hehr U Hudgins L 《American journal of medical genetics. Part A》2011,(9):2236-2241
We report on the clinical findings in siblings affected by the recently characterized X-linked form of hereditary cardiac valvular dystrophy or cardiac valve disease (OMIM 314400) due to mutations in the FLNA gene and review the literature on this condition. Although FLNA related cardiac valve disease is presumed to be a rare disorder, it is likely underdiagnosed. Several features of this condition may aid in its identification. FLNA related valvular disease can be recognized on the basis of its distinctive inheritance, early age of onset, and frequent multi-valve involvement. 相似文献
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Shu‐Bing Zhang Yu‐Xing Liu Liang‐Liang Fan Hao Huang Jing‐Jing Li Jie‐Yuan Jin Rong Xiang 《Annals of human genetics》2019,83(2):95-99
Dilated cardiomyopathy (DCM) is a relatively frequent myocardial disease that may lead to heart failure, syncope, and sudden cardiac death. Genetic factors play important roles in the etiology of the disease. To date, at least 50 genes have been identified in patients with DCM, among them, only three mutations have been reported in Synemin (SYNM) gene. In this study, we investigate a Chinese family of three generations with four patients with DCM. Employing whole‐exome sequencing (WES) and bioinformatics strategies, a novel heterozygous missense mutation p.(Trp538Arg) of SYNM was identified and cosegregated with the affected family members. The missense mutation locates in the C‐terminal domain of SYNM and leads to a substitution of tryptophan by arginine and may cause the structure change of synemin protein. In conclusion, we employed WES to detect the mutations of DCM patients and identified a novel likely pathogenic mutation in SYNM gene. Our study not only expands the spectrum of SYNM mutations, it further confirms that mutations in SYMN may underlie nonfamilial DCM, and offers genetic testing information to additional DCM patients. 相似文献
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Sian E. Piret Caroline M. Gorvin Anne Trinh John Taylor Stefano Lise Jenny C. Taylor Peter R. Ebeling Rajesh V. Thakker 《American journal of medical genetics. Part A》2016,170(11):2988-2992
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Sho Tanaka Akira Haketa Tohru Sakimoto Masanori Abe 《Journal of clinical lipidology》2018,12(2):511-514
Apolipoprotein A-I deficiency is a rare metabolic disease characterized by an impaired reverse cholesterol transport system resulting in excessive cholesterol accumulation. Here, we discuss a case of apolipoprotein A-I deficiency caused by a carboxyl-terminal truncation mutation p.His186ProfsX46 in APOA1, which might result in increased catabolism of the mutant protein. 相似文献
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Aram Yang Jinsup Kim Ja‐Hyun Jang Chung Lee Ji‐Eun Lee Sung Yoon Cho Dong‐Kyu Jin 《Annals of human genetics》2019,83(3):160-170
Multiple osteochondromas (MOs) or hereditary multiple exostoses is a rare autosomal‐dominant disease characterized by growths of MOs, which are benign cartilage‐capped bone tumors that grow away from the growth plates. Almost 90% of MOs have a molecular explanation and 10% are unexplained. MOs are genetically heterogeneous with two causal genes on 8q24.11 (EXT1) and 11p12 (EXT2), with a higher frequency in EXT1. MO is a very rare genetic disorder, and the genotype–phenotype of MO with EXT2 mutation has not been well investigated in Korea. We present the clinical radiographic and molecular analysis of a four‐generation Korean family with 11 MO‐affected members (seven males and four females). The affected members from the third generation available for molecular analysis and their detailed medical histories showed moderate‐to‐severe phenotypes (clinical classes II–III), including bony deformities and limb misalignment with pain requiring surgical correction. The x‐rays showed MOs in multiple sites. A novel EXT2 frameshift mutation (c.590delC, p.P197Qfs*73) was revealed by targeted exome sequencing in the affected members of this family. In this article, we not only expand the phenotypic–genotypic spectrum of MOs but also highlight the phenotypic heterogeneity in a family with the same mutation. In addition, we compiled the mutation spectrum of EXT2 from a literature review and identified that exon 2 of EXT2 is a mutation hot spot. Early medical attention with diagnosis of MO through careful examination of the clinical manifestations and genetic analysis can provide the opportunity to establish coordinated multispecialty management of the patient. 相似文献