Abstract:
:The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Karolak JA,Szafranski P,Kilner D,Patel C,Scurry B,Kinning E,Chandler K,Jhangiani SN,Coban Akdemir ZH,Lupski JR,Popek E,Stankiewicz Pdoi
10.1111/cge.13605subject
Has Abstractpub_date
2019-10-01 00:00:00pages
366-370issue
4eissn
0009-9163issn
1399-0004journal_volume
96pub_type
杂志文章abstract::Disorders of sex development (DSD) are rare disorders in which there is discordance between chromosomal, gonadal, and phenotypic sex. Only a minority of patients clinically diagnosed with DSD obtains a molecular diagnosis, leaving a large gap in our understanding of the prevalence, management, and outcomes in affected...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2012.01879.x
更新日期:2013-01-01 00:00:00
abstract::In 100 children with Down syndrome (DS), the parental origin of the supernumery chromosome 21 was investigated. In 76 out of the 100 cases the polymorphic regions were informative, i.e. the nondisjunction could be traced. Assessment of the alpha 1-antitrypsin/alpha 1-protease inhibitor (PI) types in these DS children ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb01037.x
更新日期:1981-10-01 00:00:00
abstract::Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity-related genes and, in some instances, add...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13789
更新日期:2020-09-01 00:00:00
abstract::The success of biomedical research in the past few decades has led to dramatic improvements in human health and, as a result, increased life expectancy. An unexpected consequence, however, has been an increase in the number of age-related diseases and, in particular, neurodegenerative diseases. Despite their prevalenc...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2005.00448.x
更新日期:2005-06-01 00:00:00
abstract::The presence of Y chromosome sequences in Turner syndrome (TS) patients may predispose them to gonadoblastoma formation with an estimated risk of 15-25%. The aim of this study was to determine the presence and the incidence of cryptic Y chromosome material in the genome of TS patients. The methodology involved a combi...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb02691.x
更新日期:1998-04-01 00:00:00
abstract::Single nucleotide polymorphisms (SNPs) are genetic variations that contribute to human phenotypes associated with various diseases. SNPs are involved in the regulation of a broad range of physiological and pathological processes, such as cellular senescence, apoptosis, inflammation, and immune response, by upregulatin...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.12950
更新日期:2017-09-01 00:00:00
abstract::The logistic regression model is a popular model for data analysis in epidemiological research. In this paper, we use this model to analyze genetic data collected from gene-longevity association studies. This new approach models the probability of observing one genotype as a function of the age of investigated individ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2001.600610.x
更新日期:2001-12-01 00:00:00
abstract::Galactokinase deficient fibroblasts are not distinguishable from galactosemic fibroblasts by a test suggested earlier by Hill & Puck (1973). They can be so distinguished by the test described here, since they are unable to incorporate radioactive galactose into TCA-insoluble material under normal conditions of incubat...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb01491.x
更新日期:1975-09-01 00:00:00
abstract::In a country-wide screening examination in Sweden, PKU was observed in 75 (4.5 per 1,000) and hyperphenylalaninemia in 14 (0.8 per 1,000) of a total of 16,805 patients in institutions for the mentally retarded. In the national neonatal screening program in 1965-1975, which covered nearly 1 million individuals, PKU was...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb00054.x
更新日期:1976-12-01 00:00:00
abstract::Details are presented of a boy with partial lipodystrophy. Only one male case has previously been described with this condition. The spectrum of partial lipodystrophy syndromes and the inheritance thereof are discussed in relation to our case. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1990.tb03602.x
更新日期:1990-11-01 00:00:00
abstract::Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22,+mar/46,XY,-22,+r(22)/47,XY,-22,+r(22)+mar/ 47, XY,-22,+r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and t...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03233.x
更新日期:1992-10-01 00:00:00
abstract::Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The p...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.13027
更新日期:2018-01-01 00:00:00
abstract::Germline mutations of the STK11 gene mapped to chromosome 19p13.3 are responsible for Peutz Jeghers syndrome (PJS), a dominant disorder associated with characteristic gastrointestinal hamartomatous polyps and a predisposition to various cancers. We conducted a detailed investigation of germline STK11 alterations by pr...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.1999.560207.x
更新日期:1999-08-01 00:00:00
abstract::Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a g...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb00799.x
更新日期:1984-08-01 00:00:00
abstract::Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The hear...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12760
更新日期:2016-08-01 00:00:00
abstract::The Marden-Walker syndrome is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. We report on a male patient with the clinical features of the syndrome. In addition, he had a Dandy-Walker...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1993.tb03823.x
更新日期:1993-06-01 00:00:00
abstract::The syndromic association of striae in the long bones and pelvis, together with sclerosis of the base of the skull, has been investigated in four families. Impairment of hearing and alteration in the shape of the head are the most important clinical manifestations. Spinal abnormalities are an inconsistent feature. The...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1978.tb04250.x
更新日期:1978-02-01 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::A follow-up study of 212 families for whom genetic counseling had been provided was performed to assess the effectiveness of the non-directive genetic counseling service at the Mount Sinai Medical Center in New York City. The preliminary result have been reported previously (Godmilow & Hirschhorn 1977). Of those famil...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1980.tb00106.x
更新日期:1980-01-01 00:00:00
abstract::The effect of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, traditionally associated with ischaemic heart disease (IHD), was assessed in a Spanish population. The transmission disequilibrium test (TDT) was used to determine a possible association in a sample of 101 trios of IHD patien...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2002.620309.x
更新日期:2002-09-01 00:00:00
abstract::The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndr...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.13375
更新日期:2019-02-01 00:00:00
abstract::Ezetimibe reduces plasma low-density lipoprotein (LDL) cholesterol by blocking sterol absorption in enterocytes. The NPC1L1 gene product was recently identified as the molecular target for ezetimibe, although functional details are incomplete. We used the non-response phenotype of plasma LDL cholesterol to ezetimibe t...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2004.00388.x
更新日期:2005-02-01 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::The Vietnam Era Twin Registry (VETR) is a registry of 7375 American male veteran twin pairs born between 1939 and 1955 who served in the armed forces of the United States between 1964 and 1975. Optimal use of registry data requires the determination of zygosity. Two approaches are available: analysis of blood genetic ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb02967.x
更新日期:1989-06-01 00:00:00
abstract::A linkage study was carried out in nine families with 24 males affected by X-linked recessive retinoschisis (RS), using three polymorphic DNA probes from the distal segment of Xp. Close linkage of the disease locus with markers DXS41 (probe p99-6) and DXS16 (pXUT23) was found, confirming the location of the RS gene on...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1987.tb03353.x
更新日期:1987-09-01 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::Four unrelated French cases of familial amyloid polyneuropathy are reported. Clinical onset ranged from the sixth to the ninth decade. Sensory signs were predominant initially in the lower limbs; motor changes, and in one case autonomic involvement, appeared later. Amyloid disease was clinically limited to the periphe...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1993.tb04439.x
更新日期:1993-03-01 00:00:00
abstract::The hypothalamus plays a critical role in the regulation of food intake and body weight, and recent work has defined a core circuitry in the hypothalamus that appears to mediate many of the effects of the adipocyte-derived hormone leptin on feeding and glucose homeostasis. However, until recently, little was known abo...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.2006.00684.x
更新日期:2006-10-01 00:00:00
abstract::In the present paper we report the first example of fertility in a female with isodicentric X-formation and karyotype 45,X/46,X,del(X)(pter----p21.3)/46,X,idic(X)(qter----p21.3::p21.3- ---qter). Her daughter was phenotypically almost normal and presented a 46,X,del(X)(pter----p21.3) karyotype in all examined cells. ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1988.tb02885.x
更新日期:1988-11-01 00:00:00
abstract::Fluorescent in situ hybridization with probes specific for a chromosomal subregion and chromosome-specific libraries (chromosome painting) are important new methods for assessing chromosome rearrangements. In this paper we present four patients with additional chromosomal material on chromosome 8p who have been studie...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1994.tb04024.x
更新日期:1994-04-01 00:00:00