Abstract:
:Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies which cause syncope and sudden death. LQT1, due to mutations of KCNQ1 (KVLQT1), is the most common form. This study describes the genotype-phenotype characteristics in 10 families with mutations of KCNQ1, including 5 novel mutations. One hundred and two families with a history of lethal cardiac events, 55 LQTS, 9 Brugada syndrome, 18 idiopathic ventricular fibrillation (IVF), and 20 acquired LQTS, were studied by single-strand conformational polymorphism (SSCP) and DNA sequence analyzes. Families found to have KCNQ1 mutations were phenotyped using ECG parameters and cardiac event history, and genotype-phenotype correlation was performed. No mutations were found in Brugada syndrome, IVF, or acquired LQTS families. Ten out of 55 LQTS families had KCNQ1 mutations and 62 carriers were identified. Mutations included G269S in domain S5; W305X, G314C, Y315C, and D317N in the pore region; A341E and Q357R in domain S6; and 1338insC, G568A and T587M mutations in the C-terminus. W305X, G314C, Q357R, 1338insC, and G568A, appeared to be novel mutations. Gene carriers were 26 +/- 19 years (32 females). Baseline QTc was 0.47 +/- 0.03 s (range 0.40-0.57 s) and 40% had normal to borderline QTc (< or = 0.46 s). Typical LQT1 T wave patterns were present in at least one affected member of each family, and in 73% of all affected members. A history of cardiac events was present in 19/62 (31%), 18 with syncope, 2 with aborted cardiac arrest (ACA) and six with sudden death (SD). Two out of 6 SDs (33%) occurred as the first symptom. No difference in phenotype was evident in pore vs. non-pore mutations. KCNQ1 mutations were limited to LQTS families. All five novel mutations produced a typical LQT1 phenotype. Findings emphasize (1) reduced penetrance of QTc and symptoms, resulting in diagnostic challenges, (2) the problem of sudden death as the first symptom (33% of those who died), and (3) genetic testing is important for identification of gene carriers with reduced penetrance, in order to provide treatment and to prevent lethal cardiac arrhythmias and sudden death.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Chen S,Zhang L,Bryant RM,Vincent GM,Flippin M,Lee JC,Brown E,Zimmerman F,Rozich R,Szafranski P,Oberti C,Sterba R,Marangi D,Tchou PJ,Chung MK,Wang Qdoi
10.1034/j.1399-0004.2003.00048.xsubject
Has Abstractpub_date
2003-04-01 00:00:00pages
273-82issue
4eissn
0009-9163issn
1399-0004pii
048journal_volume
63pub_type
杂志文章abstract::Aicardi-Goutières Syndrome is caused by IFIH1 mutations Oda et al.(2014) The American Journal of Human Genetics 95(1): 121-125. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling Rice et al.(2014) Nature Genetics 46(5): 503-510. ...
journal_title:Clinical genetics
pub_type: 评论,杂志文章
doi:10.1111/cge.12471
更新日期:2014-11-01 00:00:00
abstract::Important insights in the process of genetic counseling can be provided by establishing levels of satisfaction. The aim of our study was to compare counselees' and counselors' satisfaction with the initial consultation in reproductive genetic counseling and to gain insight into the factors associated with their conten...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00834.x
更新日期:2007-08-01 00:00:00
abstract::A sibship consisting of three siblings, one male and two females with unrelated parents, showed a clinical syndrome including: infantile spasms with hypsarrhythmia, microcephaly, severe mental retardation and spastic quadriplegia. The pneumoencephalogram performed in two sibs showed agenesis of the corpus callosum and...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1977.tb00943.x
更新日期:1977-11-01 00:00:00
abstract::The responsibility to provide accessible, useful genetic counseling to individuals from many cultures and ethnicities arises from the increasing ethnocultural diversity of the populations served, coupled with the ethical goal of providing equal access and quality of services for all individuals. The multicultural educ...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1034/j.1399-0004.2001.590301.x
更新日期:2001-03-01 00:00:00
abstract::A sample of psychotic and prepsychotic twins is presented, based on 9000 patients born during 1930--1946 and admitted to psychiatric departments in Scania, Sweden, during the 1960's. All twins of the same sex (76 pairs) were registered and their records examined. Twenty-three complete pairs, where one or both twins sh...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb00728.x
更新日期:1981-05-01 00:00:00
abstract::HLA-A and -B alleles in 74 Danish patients and 21 homozygous relatives with idiopathic haemochromatosis (IH) were compared with those in a sample of 1719 chromosomes from healthy Danish control subjects. The following alleles occurred with higher frequencies in IH compared to controls: A3: 53.6% vs. 15.1% (Pc less tha...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03619.x
更新日期:1992-01-01 00:00:00
abstract::Two brothers presented from birth with features characteristic of Sotos syndrome (cerebral gigantism): overgrowth, craniofacial abnormalities, and mental retardation with hyperactive and aggressive behavior. X-ray examination of the hands revealed imbalanced and advanced skeletal age in one, whereas anterior fontanel ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1980.tb01787.x
更新日期:1980-12-01 00:00:00
abstract::A 28-year-old woman who complained of irregular menstruation was diagnosed as suffering from trisomy 18 mosaicism. She was karyotyped because of her characteristic face, mild mental retardation and aberrant hyperpigmentation of the skin. Her motor function was within normal range. Physical and laboratory examinations,...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1996.tb04335.x
更新日期:1996-02-01 00:00:00
abstract::We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12441
更新日期:2015-07-01 00:00:00
abstract::Red hair color (RHC) was studied in a Danish material of normal families that was tested earlier for 65 marker systems. We found 4.85% of the parents to be red-haired or to have been so early in life. Scoring RHC for linkage as an autosomal dominant against blond and as hypostatic to dark hair gave a lod score of z = ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1987.tb03339.x
更新日期:1987-08-01 00:00:00
abstract::This report compares the pathogenetic influences of selective deletion and triplicaton of chromosome 13 derived from a familial 12;13 insertional translocation. In the proband a heritable chromosomal basis for his bilateral retinoblastomas is established [46,XY,del (13) (pter leads to q12.5: :q22.1 leads to qter)mat],...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1979.tb01743.x
更新日期:1979-04-01 00:00:00
abstract::A 27-year-old male with hypomelanosis of Ito (HI) is reported. One of his two children had a postaxial ray defect of one leg but neither had cutaneous features of HI. Somatic mosaicism for a gene defect lethal to ectodermal derivatives offers the best explanation for HI in males, with consequent negligible recurrence ...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1988.tb02845.x
更新日期:1988-08-01 00:00:00
abstract::The Coffin-Lowry syndrome (CLS) is a rare X-linked semidominant syndrome characterized by severe psychomotor retardation, facial dysmorphism, digit abnormalities and progressive skeletal deformations. CLS is caused by mutations in a gene located in Xp22.2, RPS6KA3. This gene encodes for a growth factor-regulated serin...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2006.00660.x
更新日期:2006-08-01 00:00:00
abstract::The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were det...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2009.01276.x
更新日期:2009-11-01 00:00:00
abstract::A case of mosaic trisomy 8 is described and the accuracy of flask culture and in situ culture techniques in detecting chromosomal mosaicism in tissues discussed. The advantages of the in situ method are illustrated and the importance of mixed colonies in defining mosaicism highlighted. The implications for prenatal di...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01989.x
更新日期:1984-03-01 00:00:00
abstract::Sudden cardiac death (SCD) has an enormous impact on those who are left behind, evoking strong feelings of anxiety and incomprehension because such a dramatic event was not anticipated. Moreover, over the last decade a prominent genetic contribution to the pathogenesis of SCD has been unveiled. As many inherited cardi...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.12519
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Chromosomal microarray analysis is the first-tier test for the evaluation of developmental disabilities and congenital anomalies. In this report, we present CMA results of 971 patient and 301 parent samples. MATERIALS AND METHODS:Among 971 patient samples, 133 (13.6%) had pathogenic variants. RESULTS:While...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12978
更新日期:2017-10-01 00:00:00
abstract::Chromosome analysis of G-banded cells from 92 individuals consecutively referred to the Cytogenetics Laboratory show that the paracentromeric band in the short arm (6p11), which stains negatively with G-banding and darkly with C-banding, shows a marked increase in size in about 9% of chromosome no. 6. The results of t...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1979.tb01761.x
更新日期:1979-02-01 00:00:00
abstract::Charcot-Marie-Tooth disease (CMT) is classified into two types, the demyelinating (CMT1) and axonal forms (CMT2). CMT2 is further subdivided by linkage analysis into eight subgroups. Recently, mutations in the MFN2 gene, which encodes the mitochondrial GTPase mitofusin 2 (Mfn2) that regulates the mitochondrial network...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00763.x
更新日期:2007-03-01 00:00:00
abstract::Autosomal dominant EEC syndrome consists of ectrodactyly, ectodermal dysplasia, and cleft lip with or without cleft palate (CL/P). We investigated an EEC kindred with 10 affected persons in three generations in order to map the causative mutation in this family and to map modifier genes that contribute to the expressi...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2004.00287.x
更新日期:2004-09-01 00:00:00
abstract::Noonan syndrome (NS) is a congenital abnormality that affects multiple parts of the body. Approximately 50% of cases are caused by mutations in the PTPN11 gene. NS shares many clinical features with a group of developmental disorders including Costello syndrome and cardio-facio-cutaneous (CFC) syndrome. Recently, KRAS...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00839.x
更新日期:2007-08-01 00:00:00
abstract::A family is reported with an autosomal dominant inherited syndrome presenting some of the typical features of the tricho-rhino-phalangeal syndrome type II (TRP II) or Langer-Giedion syndrome. The critical region for the expression of the syndrome seems to be at band 8q24.1. In the affected members of the family report...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1985.tb02045.x
更新日期:1985-06-01 00:00:00
abstract::Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12348
更新日期:2015-02-01 00:00:00
abstract::Genetic diseases in the Tunisian population represent a real problem of public health as their spectrum encompasses more than 400 disorders. Their frequency and distribution in the country have been influenced by demographic, economic and social features especially consanguinity. In this article, we report on genetic ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12616
更新日期:2016-03-01 00:00:00
abstract::Two novel missense mutations, 1939G to A (R518Q) and 2017A to G (Q544R) were identified in Japanese patients with adrenoleukodystrophy (ALD). They are located in exon 6, which encodes part of the putative adenosine triphosphate binding domain of ALD protein. The ALD protein carrying the R518Q mutation was undetectable...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1997.tb02481.x
更新日期:1997-05-01 00:00:00
abstract::An MYH2 mutation p.(Glu706Lys) was originally described in a family with autosomal dominant inheritance, where the affected family members presented with multiple congenital contractures and ophthalmoplegia, progressing to a proximal myopathy in adulthood. Another patient with a dominant mutation p.(Leu1870Pro) was de...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12552
更新日期:2015-12-01 00:00:00
abstract::Fibroblast low density lipoprotein (LDL) plasma membrane receptor activity, measured as 125I-LDL association (plasma membrane binding plus intracellular accumulation) and degradation was determined in cell strains from 14 monozygotic (MZ) and 21 like-sexed dizygotic (DZ) normolipidemic twin pairs. The twins were betwe...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:
更新日期:1981-08-01 00:00:00
abstract::FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13715
更新日期:2020-05-01 00:00:00
abstract::We describe a family in which three sibs are compound heterozygotes for two rather rare CFTR splice-site mutations, the 621 + 1G-->T and the 711 + 1G-->T mutations. Little phenotypic variation was observed between sibs, of whom two are deceased. Their disease is characterized by pancreatic insufficiency, a severe pulm...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1997.tb02456.x
更新日期:1997-03-01 00:00:00
abstract::GNE myopathy or hereditary inclusion body myopathy (HIBM) is an ultra-rare severely disabling autosomal recessive adult onset muscle disease which affects roughly one to three individuals per million worldwide. Genetically, HIBM is caused by mutations in the glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine k...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12086
更新日期:2013-12-01 00:00:00