Abstract:
:Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Although excessive spontaneous chromatid breakage has been reported in DC, it is not a consistent cytological marker for this disorder. We examined the frequency and specificity of X-irradiation-induced G2 chromatid breakage in fibroblasts from three unrelated DC patients (two males and one female). Metaphase cells from DC patients had significantly more chromatid breaks (16-18-fold and 17-26-fold at 50 and 100 rad X-irradiation, respectively) and chromatid gaps (10-12-fold and 6-7-fold at 50 and 100 rad, respectively) than those from two different controls. Analysis of banded chromosomes revealed a nonrandom distribution of chromatid aberrations in DC but not in controls, a distribution corresponding to some of the known breakpoints for cancer-specific rearrangements, constitutive fragile sites, and/or loci for cellular proto-oncogenes. The significance of this finding for cancer predisposition in DC patients is uncertain, but the increased susceptibility of X-irradiation-induced chromatid breakage may serve as a cellular marker of diagnostic value.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
DeBauche DM,Pai GS,Stanley WSsubject
Has Abstractpub_date
1990-02-01 00:00:00pages
350-7issue
2eissn
0002-9297issn
1537-6605journal_volume
46pub_type
杂志文章abstract::Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301872
更新日期:1998-06-01 00:00:00
abstract::Joubert syndrome is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation. Even within sibships the phenotype may vary, makin...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302655
更新日期:1999-12-01 00:00:00
abstract::Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective-tissue disorders characterized by skin fragility, joint laxity, and skeletal deformities. Type V collagen appears to have a causal role in EDS types I and II, which show phenotypic overlap and may sometimes be allelic. Type V collagen can exist as a h...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301948
更新日期:1998-08-01 00:00:00
abstract::The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism. From 5% to 10% of Caucasians designated as poor metabolizers (PMs) of the debrisoquine/sparteine polymorphism have a severely impaired capacity to metabolize more than 25 therapeutically u...
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::X chromosome inactivation results in the random transcriptional silencing of one of the two X chromosomes early in female development. After random inactivation, certain deleterious X-linked mutations can create a selective disadvantage for cells in which the mutation is on the active X chromosome, leading to X inacti...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302286
更新日期:1999-03-01 00:00:00
abstract::Familial adenomatous polyposis (FAP) is a premalignant disease inherited as an autosomal dominant trait, characterized by hundreds to thousands of polyps in the colorectal tract. Recently, the syndrome has been shown to be caused by mutations in the APC (adenomatous polyposis coli) gene located on chromosome 5q21. We ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::Animal microRNAs (miRNAs) regulate gene expression through base pairing to their targets within the 3' untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. We mapped annotated SNPs onto a collection of experimentally sup...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/519979
更新日期:2007-08-01 00:00:00
abstract::Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of ch...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/507652
更新日期:2006-09-01 00:00:00
abstract::An expanded G4C2 repeat in C9orf72 represents the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). However, the lower limit for pathological expansions is unknown (the suggested cutoff is 30 repeats). It has been proposed that the expansion might have...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.04.016
更新日期:2015-06-04 00:00:00
abstract::Primary microcephaly is thought to result from genetic defects of the developmental program that generates large brain hemispheres in humans. Autosomal recessive inheritance is likely in most familial cases, and four loci were recently mapped by homozygosity. We report homozygosity mapping of a new locus, MCPH5, with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/316909
更新日期:2000-12-01 00:00:00
abstract::Despite the growing consensus on the importance of testing gene-gene interactions in genetic studies of complex diseases, the effect of gene-gene interactions has often been defined as a deviance from genetic additive effects, which is essentially treated as a residual term in genetic analysis and leads to low power i...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/508571
更新日期:2006-11-01 00:00:00
abstract::Otopalatodigital syndrome type 1 (OPD1) is an X-linked semidominant condition characterized by malformations of the skeleton, auditory apparatus, and palate. Previous studies have established linkage to a 16-cM region of Xq27-q28. A proposed allelic variant of OPD1, termed "OPD2," is associated with a more severe, fre...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321280
更新日期:2001-07-01 00:00:00
abstract::A mutation involving an A-to-G nucleotide replacement at position 985 of the medium-chain acyl-CoA dehydrogenase (MCAD) cDNA was found in homozygous form in 18 unrelated MCAD-deficient families and in heterozygous form in 4 families. By PCR amplification and sequencing of cDNA from a compound heterozygote, we have det...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Neuroblastoma is a cancer of the developing sympathetic nervous system. It is diagnosed in 600-700 children per year in the United States and accounts for 12% of pediatric cancer deaths. Despite recent advances in our understanding of this malignancy's complex genetic architecture, the contribution of rare germline va...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.07.020
更新日期:2019-09-05 00:00:00
abstract::Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation that is characterized, in male patients, by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological hand aspects exhibited by patients are essential clues for the diag...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/340607
更新日期:2002-06-01 00:00:00
abstract::The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotype...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Interleukin-12 (IL12) is a cytokine that is secreted by activated phagocytes and dendritic cells and that induces interferon-gamma production by natural-killer and T lymphocytes. It consists of two subunits, p35 and p40, which are encoded by IL12A and IL12B, respectively. The first reported patient with a genetic cyto...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338625
更新日期:2002-02-01 00:00:00
abstract::Six closely linked PRP (proline-rich protein) genes code for many salivary PRPs that show frequent length and null variants. From determined protein sequences and DNA sequence analysis of variant alleles, we here report the coding and molecular basis for Con (concanavalin A-binding) and Po (parotid "o") protein polymo...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Recent studies have suggested that a significant fraction of the human genome is contained in blocks of strong linkage disequilibrium, ranging from ~5 to >100 kb in length, and that within these blocks a few common haplotypes may account for >90% of the observed haplotypes. Furthermore, previous studies have suggested...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/382227
更新日期:2004-04-01 00:00:00
abstract::We performed a genomewide linkage analysis of six separate measurements of body mass index (BMI) taken over a span of 28 years, from 1971 to 1998, in the Framingham Heart Study. Variance-components linkage analysis was performed on 330 families, using 401 polymorphic markers. The number of individuals with data at eac...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/343822
更新日期:2002-11-01 00:00:00
abstract::Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-g...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.08.013
更新日期:2018-10-04 00:00:00
abstract::Gilles de la Tourette syndrome is a neuropsychiatric disorder characterized by waxing and waning multiple motor and phonic tics with a complex mode of inheritance. Previous attempts, which used large multigenerational families to localize susceptibility loci, have been unsuccessful. In this report, the results of the ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302613
更新日期:1999-11-01 00:00:00
abstract::X-linked forms of retinitis pigmentosa (XLRP) are among the most severe, because of their early onset, often leading to significant vision loss before the 4th decade. Previously, the RP15 locus was assigned to Xp22, by linkage analysis of a single pedigree with "X-linked dominant cone-rod degeneration." After clinical...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/303091
更新日期:2000-10-01 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::Utilizing a fluorescent technique for the localization of transglutaminase activity after electrophoresis on thin layer agarose gels, we observed a new polymorphism of coagulation factor XIII in both platelets and plasma. The electrophoretic pattern was that of a dimeric protein. Homozygotes gave a single band, while ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:10.1086/425285
更新日期:2004-11-01 00:00:00
abstract::Mutations in several genes encoding components of the SWI/SNF chromatin remodeling complex cause neurodevelopmental disorders (NDDs). Here, we report on five individuals with mutations in SMARCD1; the individuals present with developmental delay, intellectual disability, hypotonia, feeding difficulties, and small hand...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.02.001
更新日期:2019-04-04 00:00:00
abstract::A non-Jewish family is presented in which the genes for Tay-Sachs disease and Sandhoff disease are segregating. Individuals heterozygous for both alleles have low serum and white cell total hexosaminidase levels together with a proportion of heat-labile hexosaminidase A (HEX A) which falls in the normal range. The ind...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::Stickler syndrome is a dominantly inherited disorder characterized by arthropathy, midline clefting, hearing loss, midfacial hypoplasia, myopia, and retinal detachment. These features are highly variable both between and within families. Mutations causing the disorder have been found in the COL2A1 and COL11A1 genes. P...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/S0002-9297(07)62938-3
更新日期:2000-11-01 00:00:00
abstract::Craniofrontonasal syndrome (CFNS) is an X-linked disorder that exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis, and additional minor malformations, but males are usually mildly affected with hypertelorism only. Despite this, males appe...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/504440
更新日期:2006-06-01 00:00:00