Abstract：
:Hereditary gingival fibromatosis (HGF) is a rare, autosomal dominant form of gingival overgrowth. Affected individuals have a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of the oral masticatory mucosa. Genetic loci for autosomal dominant forms of HGF have been localized to chromosome 2p21-p22 (HGF1) and chromosome 5q13-q22 (HGF2). To identify the gene responsible for HGF1, we extended genetic linkage studies to refine the chromosome 2p21-p22 candidate interval to approximately 2.3 Mb. Development of an integrated physical and genetic map of the interval identified 16 genes. Sequencing of these genes, in affected and unaffected HGF1 family members, identified a mutation in the Son of sevenless-1 (SOS1) gene in affected individuals. In this report, we describe the genomic structure of the SOS1 gene and present evidence that insertion of a cytosine between nucleotides 126,142 and 126,143 in codon 1083 of the SOS1 gene is responsible for HGF1. This insertion mutation, which segregates in a dominant manner over four generations, introduces a frameshift and creates a premature stop codon, abolishing four functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein. The resultant protein chimera contains the wild-type SOS1 protein for the N-terminal amino acids 1-1083 fused to a novel 22-amino acid carboxyl terminus. Similar SOS1 deletion constructs are functional in animal models, and a transgenic mouse construct with a comparable SOS1 chimera produces a phenotype with skin hypertrophy. Clarification of the functional role of this SOS1 mutant has implications for understanding other forms of gingival fibromatosis and corrective gingival-tissue management.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Hart TC,Zhang Y,Gorry MC,Hart PS,Cooper M,Marazita ML,Marks JM,Cortelli JR,Pallos Ddoi
10.1086/339689subject
Has Abstractpub_date
2002-04-01 00:00:00pages
943-54issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60301-2journal_volume
70pub_type
杂志文章abstract：:Génin and Clerget-Darpoux recently discussed the derivation of the probabilities of identity states for populations in which there was some degree of kinship, primarily to allow the extension of the classical affected-sib-pair method to such populations. It is argued here that their derivation makes certain assumption...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301743
更新日期：1998-03-01 00:00:00
abstract：:A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide sc...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/423900
更新日期：2004-09-01 00:00:00
abstract：:Monoamine oxidase (MAO) is a critical enzyme in the degradative deamination of biogenic amines throughout the body. Two biochemically distinct forms of the enzyme, A and B, are encoded in separate genes on the human X chromosome. In these studies we investigated the role of the structural gene for MAO-A in determining...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Allelic data for the D1S80 locus was obtained by using the PCR and subsequent analysis with a high-resolution, horizontal PAGE technique and silver staining. Compared with RFLP analysis of VNTR loci by Southern blotting, the approach described in this paper offers certain advantages: (1) discrete allele resolution, (2...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:We report here an evaluation of 55 pregnancies at risk for a sickle hemoglobinopathy prenatally diagnosed by restriction-endonuclease analysis, with the endonucleases MstII and HpaI, of amniocyte DNA. The diagnosis was completed in all cases. Eleven fetuses were predicted to be affected, of which six were terminated. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:Phenotypes are rarely consistent across genetic backgrounds and environments, but instead vary in many ways depending on allelic variants, unlinked genes, epigenetic factors, and environmental exposures. In the extreme, individuals carrying the same causal DNA sequence variant but on different backgrounds can be class...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2017.06.004
更新日期：2017-08-03 00:00:00
abstract：:Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/377156
更新日期：2003-08-01 00:00:00
abstract：:Apolipoprotein J (apo J) is a newly identified member of a growing family of proteins associated with various lipoprotein particles. Apo J is a glycoprotein which exists in the plasma associated with high-density lipoprotein subfractions which also contain apo A-I and cholesteryl ester transfer protein (CETP). We have...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:A girl with a prenatal 46,XY karyotype was born with a completely normal female phenotype, including uterus and histologically normal ovaries. In mice with a similar phenotype, the ablation of M33, an ortholog of Drosophila Polycomb, causes male-to-female sex reversal. The analysis of the human homolog of M33, Chromob...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2009.03.016
更新日期：2009-05-01 00:00:00
abstract：:Acid sphingomyelinase (ASM) is the lipid hydrolase that is deficient in types A and B Niemann-Pick disease (NPD). Here, we demonstrate that the gene encoding ASM (SMPD1) is paternally imprinted and that differential expression of the mutant alleles in patients with ASM-deficient NPD and in carriers influences the dise...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/503750
更新日期：2006-05-01 00:00:00
abstract：:Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of G...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301763
更新日期：1998-03-01 00:00:00
abstract：:Recently the second gene for autosomal dominant polycystic kidney disease (ADPKD), located on chromosome 4q21-q22, has been cloned and characterized. The gene encodes an integral membrane protein, polycystin-2, that shows amino acid similarity to the PKD1 gene product and to the family of voltage-activated calcium (an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/515497
更新日期：1997-09-01 00:00:00
abstract：:Results are presented on chromosome analyses made on 4,481 embryos or fetuses studied through chorionic villus sampling (CVS) in whom there was no known bias to presence of a chromosome abnormality except advanced parental age. We excluded from the analysis most cases in which mosaicism was diagnosed or in which there...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance ca...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Autosomal recessive Alport syndrome is a progressive hematuric glomerulonephritis characterized by glomerular basement membrane abnormalities and associated with mutations in either the COL4A3 or the COL4A4 gene, which encode the alpha3 and alpha4 type IV collagen chains, respectively. To date, mutation screening in t...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302106
更新日期：1998-11-01 00:00:00
abstract：:DNA methylation is assumed to be complementary on both alleles across the genome, although there are exceptions, notably in regions subject to genomic imprinting. We present a genome-wide survey of the degree of allelic skewing of DNA methylation with the aim of identifying previously unreported differentially methyla...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.01.014
更新日期：2010-02-12 00:00:00
abstract：:Palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11 at the constitutional t(11;22) breakpoint are predicted to induce genomic instability, which mediates the translocation. A PCR-based translocation-detection system for the t(11;22) has been developed with PCR primers flanking the PATRRs of both chromo...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303054
更新日期：2000-09-01 00:00:00
abstract：:In this report we describe the use of dystrophin analysis both in the diagnosis of Duchenne muscular dystrophy (DMD) in an aborted fetus and in genetic counseling. Our consultand's initial carrier risk, as based on family history and creatine kinase determinations, was calculated as 0.6%. DNA analysis of her family (a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not g...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.09.017
更新日期：2019-11-07 00:00:00
abstract：:Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutati...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/431313
更新日期：2005-07-01 00:00:00
abstract：:A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301862
更新日期：1998-06-01 00:00:00
abstract：:We have developed a technique called "LSSP-PCR" (low-stringency single specific primer PCR) that detects single or multiple mutations in DNA. A purified DNA fragment is submitted to PCR by using a single primer specific for one of the extremities of the fragment, under conditions of very low stringency. The primer hyb...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20....
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:The elucidation of the largely unknown transcriptome of small RNAs is crucial for the understanding of genome and cellular function. We report here the results of the analysis of small RNAs (< 50 nt) in the ENCODE regions of the human genome. Size-fractionated RNAs from four different cell lines (HepG2, HelaS3, GM0699...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.02.016
更新日期：2008-04-01 00:00:00
abstract：:Phosphatase and tensin homolog (PTEN) is a tumor suppressor frequently mutated in diverse cancers. Germline PTEN mutations are also associated with a range of clinical outcomes, including PTEN hamartoma tumor syndrome (PHTS) and autism spectrum disorder (ASD). To empower new insights into PTEN function and clinically ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.03.018
更新日期：2018-05-03 00:00:00
abstract：:Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequen...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2020.05.002
更新日期：2020-07-02 00:00:00
abstract：:It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed,...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.04.002
更新日期：2016-05-05 00:00:00
abstract：:We recently reported the absence of significant linkage of phonological coding dyslexia (PCD) to chromosome 6p23-p21.3 in 79 families with at least two affected siblings, even though linkage of dyslexia to this region has been found in four other independent studies. Whereas, in our previous analyses, we used a qualit...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302764
更新日期：2000-02-01 00:00:00
