共查询到20条相似文献,搜索用时 15 毫秒
1.
Tissue‐specific mosaicism for a lethal osteogenesis imperfecta COL1A1 mutation causes mild OI/EDS overlap syndrome 下载免费PDF全文
Sofie Symoens Wouter Steyaert Lynn Demuynck Anne De Paepe Karin E. M. Diderich Fransiska Malfait Paul J. Coucke 《American journal of medical genetics. Part A》2017,173(4):1047-1050
2.
Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome
Haruna Y Kobori A Makiyama T Yoshida H Akao M Doi T Tsuji K Ono S Nishio Y Shimizu W Inoue T Murakami T Tsuboi N Yamanouchi H Ushinohama H Nakamura Y Yoshinaga M Horigome H Aizawa Y Kita T Horie M 《Human mutation》2007,28(2):208-208
Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by periodic paralysis, mild dysmorphic features, and QT or QU prolongation with ventricular arrhythmias in electrocardiograms (ECGs). Mutations of KCNJ2, encoding the human inward rectifying potassium channel Kir 2.1, have been identified in patients with ATS. We aimed to clarify the genotype-phenotype correlations in ATS patients. We screened 23 clinically diagnosed ATS patients from 13 unrelated Japanese families. Ten different forms of KCNJ2 mutations were identified in the 23 ATS patients included in this study. Their ECGs showed normal QTc intervals and abnormal U waves with QUc prolongation and a variety of ventricular arrhythmias. Especially, bidirectional ventricular tachycardia (VT) was observed in 13 of 23 patients (57%). Periodic paralysis was seen in 13 of 23 carriers (57%), dysmorphic features in 17 (74%), and seizures during infancy in 4 (17%). Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q) and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a heterologous expression system and showed strong dominant negative effects when co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV respectively compared to wild-type alone). Immunocytochemistry and confocal imaging revealed normal trafficking for mutant channels. In our study, all of the clinically diagnosed ATS patients had KCNJ2 mutations and showed a high penetrance with regard to the typical cardiac phenotypes: predominant U wave and ventricular arrhythmias, typically bidirectional VT. 相似文献
3.
4.
5.
6.
Cystic kidneys in fetal Walker–Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature 下载免费PDF全文
Marwa M. Nabhan Nour ElKhateeb Daniela A. Braun Sungho Eun Sahar N. Saleem Heon YungGee Friedhelm Hildebrandt Neveen A. Soliman 《American journal of medical genetics. Part A》2017,173(10):2697-2702
7.
Nobuhiko Okamoto 《American journal of medical genetics. Part A》2019,179(5):822-826
Okamoto syndrome is characterized by severe intellectual disability, generalized hypotonia, stenosis of the ureteropelvic junction with hydronephrosis, cardiac anomalies, and characteristic facial gestalt. Several patients have been reported. The basic mechanism of Okamoto syndrome has not been clarified. Au–Kline syndrome is a new syndrome due to loss‐of‐function variants in the HNRNPK (heterogeneous nuclear ribonucleoprotein K) gene. A new patient with Okamoto syndrome visited our hospital. We noticed that the patient had features overlapping with Au–Kline syndrome. We studied the HNRNPK gene by Sanger sequencing, and identified a novel splicing variant. We suggest that Okamoto syndrome is identical to Au–Kline syndrome. 相似文献
8.
Further evidence for specific IFIH1 mutation as a cause of Singleton–Merten syndrome with phenotypic heterogeneity 下载免费PDF全文
Maria Pettersson Birgitta Bergendal Johanna Norderyd Daniel Nilsson Britt‐Marie Anderlid Ann Nordgren Anna Lindstrand 《American journal of medical genetics. Part A》2017,173(5):1396-1399
9.
10.
11.
Autosomal recessive IFT57 hypomorphic mutation cause ciliary transport defect in unclassified oral–facial–digital syndrome with short stature and brachymesophalangia 下载免费PDF全文
J. Thevenon S. Phadke T. Eguether A. Saunier M. Avila V. Carmignac A.‐L. Bruel J. St‐Onge Y. Duffourd G.J. Pazour B. Franco T. Attie‐Bitach A. Masurel‐Paulet J.‐B. Rivière V. Cormier‐Daire C. Philippe L. Faivre C. Thauvin‐Robinet 《Clinical genetics》2016,90(6):509-517
12.
13.
New SMARCA2 mutation in a patient with Nicolaides–Baraitser syndrome and myoclonic astatic epilepsy 下载免费PDF全文
S. Tang E. Hughes K. Lascelles M. A. Simpson D. K. Pal 《American journal of medical genetics. Part A》2017,173(1):195-199
We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with myoclonic astatic epilepsy, leading to reassessment and identification of Nicolaides–Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be associated with Nicolaides–Baraitser syndrome and adds to chromatin remodeling as a pathway for epileptogenesis. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. 相似文献
14.
Mi‐Hyun Park Hwanseok Rhee Song‐Ju Yang Kyoung‐Gyu Choi Sung‐Chul Jung Han Su Kim Young Se Hyun Khriezhanuo Nakhro Hye Jin Lee Hae‐Mi Woo Ki Wha Chung 《Human mutation》2012,33(11):1610-1615
Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neuropathies and is a genetically and clinically heterogeneous disorder with variable inheritance modes. As several molecules have been reported to have therapeutic effects on CMT, depending on the underlying genetic causes, exact genetic diagnostics have become very important for executing personalized therapy. Whole‐exome sequencing has recently been introduced as an available method to identify rare or novel genetic defects from genetic disorders. Particularly, CMT is a model disease to apply exome sequencing because more than 50 genes (loci) are involved in its development with weak genotype–phenotype correlation. This study performed the exome sequencing in 25 unrelated CMT patients who revealed neither 17p12 duplication/deletion nor several major CMT genes. This study identified eight causative heterozygous mutations (32%). This detection rate seems rather high because each sample was tested before the study for major genetic causes. Therefore, this study suggests that the exome sequencing can be a highly exact, rapid, and economical molecular diagnostic tool for CMT patients who are tested for major genetic causes. Hum Mutat 33:1610–1615, 2012. © 2012 Wiley Periodicals, Inc. 相似文献
15.
16.
Emilie Lalonde Steffen Albrecht Kevin C.H. Ha Karine Jacob Nathalie Bolduc Constantin Polychronakos Pierre Dechelotte Jacek Majewski Nada Jabado 《Human mutation》2010,31(8):918-923
Protein coding genes constitute approximately 1% of the human genome but harbor 85% of the mutations with large effects on disease‐related traits. Therefore, efficient strategies for selectively sequencing complete coding regions (i.e., “whole exome”) have the potential to contribute our understanding of human diseases. We used a method for whole‐exome sequencing coupling Agilent whole‐exome capture to the Illumina DNA‐sequencing platform, and investigated two unrelated fetuses from nonconsanguineous families with Fowler Syndrome (FS), a stereotyped phenotype lethal disease. We report novel germline mutations in feline leukemia virus subgroup C cellular‐receptor‐family member 2, FLVCR2, which has recently been shown to cause FS. Using this technology, we identified three types of genetic abnormalities: point‐mutations, insertions‐deletions, and intronic splice‐site changes (first pathogenic report using this technology), in the fetuses who both were compound heterozygotes for the disease. Although revealing a high level of allelic heterogeneity and mutational spectrum in FS, this study further illustrates the successful application of whole‐exome sequencing to uncover genetic defects in rare Mendelian disorders. Of importance, we show that we can identify genes underlying rare, monogenic and recessive diseases using a limited number of patients (n=2), in the absence of shared genetic heritage and in the presence of allelic heterogeneity. Hum Mutat 31:1–6, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
17.
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases 下载免费PDF全文
Marie Bernkopf David Hunt Nils Koelling Tim Morgan Amanda L. Collins Joanna Fairhurst Stephen P. Robertson Andrew G. L. Douglas Anne Goriely 《Human mutation》2017,38(10):1360-1364
We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence‐based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low‐level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next‐generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in ~20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence‐based counseling on reproductive safety. 相似文献
18.
Christopher M. Watson Philip Dean Nick Camm Jennifer Bates Ian M. Carr Carol A. Gardiner David T. Bonthron 《Human mutation》2020,41(2):525-531
The diagnostic deployment of massively parallel short‐read next‐generation sequencing (NGS) has greatly improved genetic test availability, speed, and diagnostic yield, particularly for rare inherited disorders. Nonetheless, diagnostic approaches based on short‐read sequencing have a poor ability to accurately detect gene conversion events. We report on the genetic analysis of a family in which 3 fetuses had clinical features consistent with the autosomal recessive disorder Meckel–Gruber syndrome (MKS). Targeted NGS of 29 known MKS‐associated genes revealed a heterozygous TMEM231 splice donor variant c.929+1A>G. Comparative read‐depth analysis, performed to identify a second pathogenic allele, revealed an apparent heterozygous deletion of TMEM231 exon 4. To verify this result we performed single‐molecule long‐read sequencing of a long‐range polymerase chain reaction product spanning this locus. We identified four missense variants that were absent from the short‐read dataset due to the preferential mapping of variant‐containing reads to a downstream TMEM231 pseudogene. Consistent with the parental segregation analysis, we demonstrate that the single‐molecule long reads could be used to show that the variants are arranged in trans. Our experience shows that robust validation of apparent dosage variants remains essential to avoid the pitfalls of short‐read sequencing and that new third‐generation long‐read sequencing technologies can already aid routine clinical care. 相似文献
19.
20.
Zeynep H. Coban‐Akdemir Wu‐Lin Charng Mahshid Azamian Ingrid S. Paine Jaya Punetha Christopher M. Grochowski Tomasz Gambin Santiago O. Valdes Bryan Cannon Gladys Zapata Patricia P. Hernandez Shalini Jhangiani Harsha Doddapaneni Jianhong Hu Fatima Boricha Donna M. Muzny Eric Boerwinkle Yaping Yang Richard A. Gibbs Jennifer E. Posey Xander H. T. Wehrens John W. Belmont Jeffrey J. Kim Christina Y. Miyake James R. Lupski Seema R. Lalani 《American journal of medical genetics. Part A》2020,182(6):1387-1399