Abstract:
:An emerging challenge facing those who are concerned about the efficacy of public health programs is to understand how information from the DNA revolution might be used to improve our ability to predict the initiation, progression and severity of a common disease having a complex multifactorial etiology. In the course of research to evaluate the role of information about DNA, combinations of genome types and environmental exposures that predispose to disease will be identified. Such information is expected to be useful in efforts to identify individuals and families at higher risk of disease and to predict their responses to a proposed therapy. This paper begins with a discussion of the features of a realistic biological model for the study of a common multifactorial disease. We present evidence for the complexity in the relationship between genome type variation and variation in risk of coronary artery disease (CAD) and review the preliminary results of our studies to determine whether information about genome type variation can improve our ability to predict the distribution of CAD among individuals in the population at large. Such studies make it apparent that new analytical strategies are necessary to deal with the plethora of genome type information available for the evaluation of risk of a common disease like CAD. This shift in the research paradigm will build upon new strategies to understand the organization of natural systems that are coming from outside the mainstream of genetic research.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Sing CF,Zerba KE,Reilly SLdoi
10.1111/j.1399-0004.1994.tb04196.xsubject
Has Abstractpub_date
1994-07-01 00:00:00pages
6-14issue
1 Spec Noeissn
0009-9163issn
1399-0004journal_volume
46pub_type
杂志文章,评审abstract::Non-mosaic males with a 46,XY karyotype and a MECP2 null mutation display a phenotype of severe neonatal-onset encephalopathy that is distinctly different from Rett syndrome (RTT). To increase awareness of this rare disorder, we are reporting novel findings in a sporadic case, compare them to 16 previously reported ca...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.2008.01005.x
更新日期:2008-08-01 00:00:00
abstract::Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored ou...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13878
更新日期:2021-02-01 00:00:00
abstract::Identifying a mutation in a heterogeneous disease such as inherited cardiomyopathy is a challenge because classical methods, like linkage analysis, can often not be applied as there are too few meioses between affected individuals. However, if affected individuals share the same causal mutation, they will also share a...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01472.x
更新日期:2011-05-01 00:00:00
abstract::Recurrent trisomy 21: four cases in three generations. While gonadal mosaicism can lead to recurrence of trisomy 21 (T21) for a single couple, the recurrence of free T21 in multiple members of a single pedigree has rarely been reported. We present an unusual pedigree with four cases of Down syndrome (DS) with free T21...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2005.00512.x
更新日期:2005-11-01 00:00:00
abstract::Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distri...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb02753.x
更新日期:1998-05-01 00:00:00
abstract::We report on an 18-month-old girl who has both the cri du chat and Marfan syndromes. She was born at term to a 29-year-old woman with the clinical diagnosis of Marfan syndrome. An evaluation for developmental delay at 2 months of age showed a karyotype of 46,XX,del(5)(15.1), consistent with cri du chat syndrome. At ag...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1994.tb04169.x
更新日期:1994-10-01 00:00:00
abstract::Approximately one in 500 individuals in Western population has autosomal dominant familial hypercholesterolemia due to mutations in the low-density lipoprotein receptor (LDLR) gene. Screening for these mutations is hampered by their large number, except in founder populations. We identified the breakpoint of the >15 k...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.0009-9163.2004.00223.x
更新日期:2004-03-01 00:00:00
abstract::Malignant hyperthermia (MH)-related mutations have been identified in the ryanodine receptor type 1 gene (RYR1) and in the dihydropyridine gene (CACNA1S), but about half of the patients do not have causative mutations in these genes. We wanted to study the contribution of other muscle genes to the RYR1 phenotypes. We ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12508
更新日期:2015-10-01 00:00:00
abstract::Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene, with apparent lethality in male embryos. However, recent studies indicate that mutations in the MECP2 gene can cause congenital encephalopathy, an Angelman-like phenotype and even nonspecific mental retardation in mal...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2002.610507.x
更新日期:2002-05-01 00:00:00
abstract::Mutations in the NPC1 or NPC2 gene are responsible for Niemann-Pick type C (NPC) disease (OMIM #257220), an autosomal recessive neurodegenerative lysosomal storage disorder caused by an incorrect regulation of intracellular lipid trafficking. A molecular analysis carried out in 30 unrelated patients identified 43 dist...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01504.x
更新日期:2011-07-01 00:00:00
abstract::Phytohaemagglutinin induces interferon-gamma synthesis in lymphocyte cultures from healthy individuals. We report two sibs with recurrent infections, selective IgA deficiency, and reduced blast transformation index under PHA-stimulation, without interferon-gamma response. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1988.tb03480.x
更新日期:1988-06-01 00:00:00
abstract::Kyphomelic dysplasia is a rare form of generalized skeletal dysplasia with about 15 cases described so far in the literature. We present the clinical, radiological, and pathological findings of an antenatally detected female fetus affected with this disorder. The differential diagnoses of prenatal and perinatal semile...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1034/j.1399-0004.2000.580510.x
更新日期:2000-11-01 00:00:00
abstract::Mental retardation affects 1-3% of the general population, and the genetic causes in many cases are unknown. Cytogenetically undetected chromosomal imbalances have been indicated as an explanation. Nowadays, due to the development of molecular cytogenetic techniques, it is possible to identify cryptic rearrangements i...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j..2004.00167.x
更新日期:2004-01-01 00:00:00
abstract::A deletion of 7q21.2-q22.1 has been found in a patient with split foot and developmental retardation. Molecular analysis using polymerase chain reaction (PCR) showed deletion of three microsatellite markers, D7S527, D7S479 and D7S554, in the patient's paternal chromosome. These results pinpoint the critical region for...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1995.tb03930.x
更新日期:1995-02-01 00:00:00
abstract::This report describes a 46,XY phenotypic female infant with absent uterus, probable agonadism, and bilateral upper amelia. The constellation of anomalies is similar to that of the patient described by Temoçin et al. (Acta Paediatr Jpn 1997: 39: 631-633), and may suggest a developmental link between genital region and ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb03693.x
更新日期:1998-07-01 00:00:00
abstract::Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autosomal-recessive autoimmune disease caused by autoimmune regulator gene mutations. The aim of this study was to examine the mutation profile of Polish APECED patients, determine the carrier rate of the most frequent mutation(s) and estima...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2006.00690.x
更新日期:2006-10-01 00:00:00
abstract::Multiple congenital malformations in a young girl with bilateral conductive hearing loss are described. Facial dysmorphic features include prominent supraorbital ridges, facial hypoplasia, facial asymmetry, downward-slanting palpebral fissures, high prominent nasal bridge with bifid nasal tip and a small lower jaw, an...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1997.tb02511.x
更新日期:1997-07-01 00:00:00
abstract::A four generation family with postaxial polydactyly of hands and feet and dental anomalies is reported. Lower and upper incisors were abnormal in shape and number. Additional findings were prominent ear anthelices, hypoplastic and dysplastic nails and mild shortness of stature. Inheritance was dominant with variable e...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01108.x
更新日期:1984-12-01 00:00:00
abstract::We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family mem...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13217
更新日期:2018-05-01 00:00:00
abstract::We describe a pedigree in which four male members are affected by a contiguous gene abnormality involving the short arm of the X chromosome (Xp22.32). Bivariate flow cytometry of lymphoblastoid cell lines from two of these individuals and a normal male showed a 6-7 megabase deletion in affected males, and high resolut...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1993.tb04442.x
更新日期:1993-04-01 00:00:00
abstract::Ectodermal dysplasias are a group of genetic disorders defined by ectodermal derivative impairment (EDI). To test the impact of the Wnt/beta-catenin pathway in the genetic screening of EDI, we performed a molecular gene study of WNT10A in 60 subjects from a population of 133 young Italian patients referred for the imp...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13147
更新日期:2018-03-01 00:00:00
abstract::Complex microphthalmia is characterized by small eyes with additional abnormalities that may include anterior segment dysgenesis. While many genes are known, a genetic cause is identified in only 4-30% of microphthalmia, with the lowest rate in unilateral cases. We identified four novel pathogenic loss-of-function all...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13897
更新日期:2020-12-13 00:00:00
abstract::Alzheimer's Disease (AD) is a devastating disease that affects millions of elderly persons. Despite years of intense investigations, genetic risk factors that affect the majority of AD cases have yet to be determined. Recent studies suggest that cholesterol metabolism has integral part in AD pathogenesis, suggesting t...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.0009-9163.2004.00280.x
更新日期:2004-07-01 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::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::Apolipoprotein C3 (APOC3) mutations carriers typically display high plasma high-density lipoprotein cholesterol (HDL-C) and low triglycerides (TGs). We set out to investigate the prevalence and clinical consequences of APOC3 mutations in individuals with hyperalphalipoproteinemia. Two novel mutations (c.-13-2A>G and c...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12201
更新日期:2014-05-01 00:00:00
abstract::A sequencing protocol for the acid beta-glucosidase (GCase) gene (GBA) was developed using a long-range PCR template. This protocol has an advantage of greater DNA yields over similar strategies. Seven Gaucher's disease patients had four novel and five other rare alleles. A non-pseudogene in-frame deletion (g.2600-260...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2003.00100.x
更新日期:2003-07-01 00:00:00
abstract::We present a case of lethal fetal akinesia deformation sequence (FADS) caused by a frameshift variant in trans with a 148 kbp deletion encompassing 3-36 exons of AGRN. Pathogenic variants in AGRN have been described in families with a form of congenital myasthenic syndrome (CMS), manifesting in the early childhood wit...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13677
更新日期:2020-04-01 00:00:00
abstract::Depression during pregnancy can have serious consequences for families. Indications of fetal aneuploidy can induce maternal stress, a risk factor for depression. Few studies have assessed symptoms of depression in pregnant women soon after they receive results indicating increased risk for fetal aneuploidy. We compare...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2008.01056.x
更新日期:2009-01-01 00:00:00
abstract::This brief account of Woody Guthrie is instructive to clinical geneticists. It tells the story of one famous man's understanding of, and struggle with, Huntington's disease. The philatelic illustration depicts Woody Guthrie playing his guitar in the years before advancement of the disease. ...
journal_title:Clinical genetics
pub_type: 传,历史文章,杂志文章
doi:10.1034/j.1399-0004.2002.610404.x
更新日期:2002-04-01 00:00:00