Abstract:
:Primary immunodeficiencies (PIDs) comprise a diverse group of over 400 genetic disorders that result in clinically apparent immune dysfunction. Although PIDs are classically considered as Mendelian disorders with complete penetrance, we now understand that absent or partial clinical disease is often noted in individuals harboring disease-causing genotypes. Despite the frequency of incomplete penetrance in PID, no conceptual framework exists to categorize and explain these occurrences. Here, by reviewing decades of reports on incomplete penetrance in PID we identify four recurrent themes of incomplete penetrance, namely genotype quality, (epi)genetic modification, environmental influence, and mosaicism. For each of these principles, we review what is known, underscore what remains unknown, and propose future experimental approaches to fill the gaps in our understanding. Although the content herein relates specifically to inborn errors of immunity, the concepts are generalizable across genetic diseases.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Gruber C,Bogunovic Ddoi
10.1007/s00439-020-02131-9subject
Has Abstractpub_date
2020-06-01 00:00:00pages
745-757issue
6-7eissn
0340-6717issn
1432-1203pii
10.1007/s00439-020-02131-9journal_volume
139pub_type
杂志文章,评审相关文献
HUMAN GENETICS文献大全abstract::A homozygous gene deletion of the glutathione S-transferase M1 (GSTM1) locus of genomic DNA from blood spots was studied by the polymerase chain reaction in a group of French heavy smokers (n = 361), which included patients with severe chronic bronchitis (SCB; n = 87), moderate chronic bronchitis (MCB: n = 102) and ha...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050455
更新日期:1997-06-01 00:00:00
abstract::Association studies for complex diseases based on pedigree haplotype or genotype data have received increasing attention in the last few years. The similarity tests are appealing for these studies because they take into account of the DNA structure, but they have blind areas on which significant association can not be...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-007-0376-5
更新日期:2007-08-01 00:00:00
abstract::X-linked hydrocephalus (HSAS) is the most common form of inherited hydrocephalus characterized by hydrocephalus due to stenosis of the aqueduct of Sylvius, mental retardation, clasped thumbs, and spastic paraparesis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked com...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02185770
更新日期:1996-03-01 00:00:00
abstract::Cytogenetic analysis of a 20-year-old sterile male revealed a 45,X0 karyotype with no evidence for Y-chromosomal material on any of the chromosomes analysed by Q-, G- and C-banding. DNA analysis with 17 different Y chromosome-derived probes revealed the presence of Yp DNA sequences in the patient's genome. In situ hyb...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF00204168
更新日期:1991-06-01 00:00:00
abstract::Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). This frequently occurs as a new mutation, manifes...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-004-1151-5
更新日期:2004-08-01 00:00:00
abstract::Thirty one families with Alport syndrome including 3 families with associated syndromes were studied. The location of the COL4A5 gene, responsible for the Alport syndrome, was determined by linkage analysis with eight probes of the Xq arm and by a radiation hybrid panel. Concordant data indicated the localization of t...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00220471
更新日期:1992-12-01 00:00:00
abstract::Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during chi...
journal_title:Human genetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00439-014-1514-5
更新日期:2015-06-01 00:00:00
abstract::Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of "haplotype-tagging" single-nucleotide polymorphisms (SNPs) that identify the most common haplotypes. These studies are motivated by the assumption that...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-004-1122-x
更新日期:2004-07-01 00:00:00
abstract::The neurofibromatosis type 1 (NF1) gene located at 17q 11.2 contains 60 exons and spans 350 kb of genomic DNA. Mutation analysis has been hampered by the large size of the gene, the high rate of new mutations, a lack of mutational clustering and the presence of numerous homologous loci. Mutation detection methods base...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004399900135
更新日期:1999-10-01 00:00:00
abstract::The p53 gene product is part of a pathway regulating growth arrest at the G1 checkpoint of the cell cycle. Mutation of other components of this pathway, including the products of the ataxia telangiectasia (AT), GADD45, mdm2, and p21WAF1/CIP1 genes may have effects comparable to mutations in the p53 gene. The GADD45 ge...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02267084
更新日期:1996-04-01 00:00:00
abstract::Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, oppo...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1455-z
更新日期:2014-09-01 00:00:00
abstract::Three patients with 45,X/46,XYnf mosaicism were investigated by Southern hybridization using both X- and Y-specific DNA probes. Our patients seem to be hemizygous for the X chromosomal loci tested. Single-copy and low-copy repeated Y chromosomal sequences assigned to the short arm, centromere, and euchromatin of the l...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284913
更新日期:1987-06-01 00:00:00
abstract::X chromosome inactivation results in dosage equivalency for X-linked gene expression between males and females. However, some X-linked genes show variable X inactivation, being expressed from the inactive X in some females but subject to inactivation in other women. The human tissue inhibitor of metalloproteinases-1 (...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-002-0676-8
更新日期:2002-03-01 00:00:00
abstract::Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, as well as syndromal associations. These conditions have a significant impact on vision due to disruption of the visual axis, and al...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-018-1935-7
更新日期:2019-09-01 00:00:00
abstract::By a general survey in the hopitals of northeast Italy, Duchenne cases have been located and identified over a 20-year period. In a more restricted area screening for Duchenne carriers has been carried out in affected families. This procedure made possible an exact estimate of the incidence rate, prevalence rate, and ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00393974
更新日期:1977-02-11 00:00:00
abstract::A total of 1242 individuals from six Chinese ethnic groups were studied with respect to the glyoxalase I polymorphism using agarose gel electrophoresis. The GLO1*1 gene frequency and the number of subjects tested in each population are as follows: Uygur 0.2466 (219), Hui 0.1621 (219), Dong 0.1866 (201), Bai 0.1921 (20...
journal_title:Human genetics
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::Family-based candidate gene and genome-wide association studies are a logical progression from linkage studies for the identification of gene and polymorphisms underlying complex traits. An efficient way to analyse phenotypic and genotypic data is to model linkage and association simultaneously. An important result fr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0278-y
更新日期:2007-03-01 00:00:00
abstract::The secondary constriction in human chromosome 1 consists of a proximal segment stained by the GC-specific fluorochrome mithramycin and a distal segment stained by such fluorochromes as DAPI or DIPI, which show enhanced fluorescence intensities in AT-rich regions of the chromosomes. A study involving 21 individuals re...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278895
更新日期:1979-01-19 00:00:00
abstract::During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5' end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompas...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00202819
更新日期:1994-05-01 00:00:00
abstract::Transient neonatal diabetes mellitus (TNDM) is associated with overexpression of an imprinted locus on chromosome 6q24; this locus contains a differentially methylated region (DMR) consisting of an imprinted CpG island that normally allows expression only from the paternal allele of genes under its control. Three type...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-004-1236-1
更新日期:2005-03-01 00:00:00
abstract::Microsatellite markers RS46 (DXS548) and FRAXAC2 flanking the fragile X mutation, an expansion of a (CGG)n repeat within the FMR-1 gene, were typed in 60 unrelated northern and eastern Finnish fragile X families and in a control population from the same geographical region. A significant difference was found in alleli...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00211011
更新日期:1994-11-01 00:00:00
abstract::Neural tube defect disorders are developmental diseases that originate from an incomplete closure of the neural tube during embryogenesis. Despite high prevalence-1 out of 3000 live births-their etiology is not yet established and both environmental and genetic factors have been proposed, with a heritability rate of a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-019-01993-y
更新日期:2019-04-01 00:00:00
abstract::Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-010-0897-1
更新日期:2011-01-01 00:00:00
abstract::The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are c...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00420946
更新日期:1993-12-01 00:00:00
abstract::The delta F508 mutation and cystic fibrosis (CF) haplotypes with the markers KM19, pMP6d-9 and J3.11 are described in 54 adult British CF patients. delta F508 was found on 70% of all CF chromosomes, on none of the normal chromosomes and on only 37.5% of pancreatic sufficient CF chromosomes. All patients with meconium ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02428295
更新日期:1990-09-01 00:00:00
abstract::Chromosomal studies of the bone marrow and cultured peripheral blood cells in a 42-year-old female with the clinical and laboratory features typical for CML revealed a previously undescribed variant translocation involving chromosomes 12 and 22. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00287017
更新日期:1977-11-10 00:00:00
abstract::Lower plasma levels of high-density lipoprotein cholesterol (HDL-C) are associated with the metabolic syndrome (insulin resistance, obesity, hypertension) and higher cardiovascular risk. Recent association studies have suggested rare alleles responsible for very low HDL-C levels. However, for individual cardiovascular...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0167-4
更新日期:2006-06-01 00:00:00
abstract::In the Original article published, the figure number 5: Genomic distribution of ROH is incorrectly published. The correct figure is given below. ...
journal_title:Human genetics
pub_type: 已发布勘误
doi:10.1007/s00439-019-02053-1
更新日期:2019-10-01 00:00:00
abstract::The most commonly accepted view about the origin of aneuploidy is that it is due to errors in meiotic division. However, its rare occurrence makes it difficult to explain recurrent births of trisomic children to some parents. This problem causes more serious concern when one accepts that an abnormal (n + 1 or n - 1) s...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00286609
更新日期:1984-01-01 00:00:00
abstract::TransferrinC (TfC) subtypes were determined by isoelectric focusing (PAGIF) on samples from 90 carriers of the TFB and TfD alleles. In all cases of CB and CD heterozygotes only one of the two common subtypes of the TfC allele, TfC1 or TfC2, was observed. This is considered strong support for the hypothesis of two comm...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278905
更新日期:1979-01-19 00:00:00