Abstract:
:Brachydactyly type B (BDB) is an autosomal dominant skeletal disorder characterized by hypoplasia/aplasia of distal phalanges and nails. Recently, heterozygous mutations of the orphan receptor tyrosine kinase (TK) ROR2, located within a distinct segment directly after the TK domain, have been shown to be responsible for BDB. We report four novel mutations in ROR2 (two frameshifts, one splice mutation, and one nonsense mutation) in five families with BDB. The mutations predict truncation of the protein within two distinct regions immediately before and after the TK domain, resulting in a complete or partial loss of the intracellular portion of the protein. Patients affected with the distal mutations have a more severe phenotype than do those with the proximal mutation. Our analysis includes the first description of homozygous BDB in an individual with a 5-bp deletion proximal to the TK domain. His phenotype resembles an extreme form of brachydactyly, with extensive hypoplasia of the phalanges and metacarpals/metatarsals and absence of nails. In addition, he has vertebral anomalies, brachymelia of the arms, and a ventricular septal defect-features that are reminiscent of Robinow syndrome, which has also been shown to be caused by mutations in ROR2. The BDB phenotype, as well as the location and the nature of the BDB mutations, suggests a specific mutational effect that cannot be explained by simple haploinsufficiency and that is distinct from that in Robinow syndrome.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Schwabe GC,Tinschert S,Buschow C,Meinecke P,Wolff G,Gillessen-Kaesbach G,Oldridge M,Wilkie AO,Kömec R,Mundlos Sdoi
10.1086/303084subject
Has Abstractpub_date
2000-10-01 00:00:00pages
822-31issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63276-5journal_volume
67pub_type
杂志文章abstract::Gap junctions are assemblies of intercellular channels that regulate a variety of physiologic and developmental processes through the exchange of small ions and signaling molecules. These channels consist of connexin family proteins that allow for diversity of channel composition and conductance properties. The human ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/346090
更新日期:2003-02-01 00:00:00
abstract::The chitinase 3-like 1 gene (CHI3L1) is abnormally expressed in the hippocampus of subjects with schizophrenia and may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia. Here, we provide evidence that the functional variants at the CHI3L1 locus...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/510438
更新日期:2007-01-01 00:00:00
abstract::The polymerase chain reaction (PCR) makes it possible to rapidly generate a very large number of copies of a specific region of DNA. Application of PCR to individual human sperm cells permits the typing of a large number of independent male meiotic events. If the donor male is heterozygous at three loci, sperm typing ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Fuchs endothelial corneal dystrophy (FECD) is a common disease for which corneal transplantation is the only treatment option in advanced stages, and alternative treatment strategies are urgently required. Expansion (≥50 copies) of a non-coding trinucleotide repeat in TCF4 confers >76-fold risk for FECD in our large c...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.02.010
更新日期:2018-04-05 00:00:00
abstract::Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring w...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-exp...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.03.002
更新日期:2016-05-05 00:00:00
abstract::Two familial and seven sporadic patients with neurofibromatosis 1-who showed dysmorphism, learning disabilities/mental retardation, and additional signs and carried deletions of the NF1 gene-were investigated by use of a two-step FISH approach to characterize the deletions. With FISH of YAC clones belonging to a 7-Mb ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302709
更新日期:2000-01-01 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::Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we exa...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/521051
更新日期:2007-10-01 00:00:00
abstract::Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six proband...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/503204
更新日期:2006-04-01 00:00:00
abstract::To assess the association between recombination and nondisjunction of chromosome 21, we analyzed cytogenetic and DNA markers in 104 trisomy 21 individuals and their parents. Our DNA marker studies of parental origin were informative in 100 cases, with the overwhelming majority (94) being maternal in origin. This value...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::When the mode of inheritance of a disease is unknown, the LOD-score method of linkage analysis must take into account uncertainties in model parameters. We have previously proposed a parametric linkage test called "MFLOD," which does not require specification of disease model parameters. In the present study, we intro...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302888
更新日期:2000-05-01 00:00:00
abstract::Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 off...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract::Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.04.018
更新日期:2013-06-06 00:00:00
abstract::Autism is a heritable but genetically complex disorder characterized by deficits in language and in reciprocal social interactions, combined with repetitive and stereotypic behaviors. As with many genetically complex disorders, numerous genome scans reveal inconsistent results. A genome scan of 345 families from the A...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/430278
更新日期:2005-06-01 00:00:00
abstract::Linkage analysis of 72 pedigrees by the maximum-likelihood method provides evidence of linkage between HLA and the hypothesized multiple sclerosis susceptibility gene (MSSG) for both the dominant and recessive models of inheritance and for penetrance values ranging from 5%--65% (or higher). This MSSG, if it exists, is...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::Allele-specific replication differences have been observed in imprinted chromosomal regions. We have exploited this characteristic of an imprinted region by using FISH at D15S9 and SNRPN (small nuclear ribonucleo protein N) on interphase nuclei to distinguish between Angelman and Prader-Willi syndrome patient samples ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::A single base mutation at nucleotide position 3460 (nt 3460) in the ND1 gene in human mtDNA was found to be associated with Leber hereditary optic neuroretinopathy (LHON). The G-to-A mutation converts an alanine to a threonine at the 52d codon of the gene. The mutation also abolishes an AhaII restriction site and thus...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, trackin...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:10.1016/j.ajhg.2007.12.001
更新日期:2008-01-01 00:00:00
abstract::Over the past 20 years, the focus of national efforts to improve K-12 science education has ranged from curriculum and professional development of teachers to the adoption of science standards and high-stakes testing. In spite of this work, students in the United States continue to lag behind their peers in other coun...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.05.010
更新日期:2009-07-01 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::Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301969
更新日期:1998-08-01 00:00:00
abstract::Recently, to speed up the differential-diagnosis process based on symptoms and signs observed from an affected individual in the diagnosis of rare diseases, researchers have developed and implemented phenotype-driven differential-diagnosis systems. The performance of those systems relies on the quantity and quality of...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.08.003
更新日期:2018-09-06 00:00:00
abstract::Comparisons are presented of the ages of onset of 20 cases of hereditary medullary carcinoma of the thyroid (MCT) and of 22 sporadic cases of this same type of cancer. These data are compatible with what might be expected by the two-mutational-event theory of the initiation of cancer postulated by Knudson. It had been...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract::Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-an...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2012.08.021
更新日期:2012-10-05 00:00:00
abstract::Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases involving the abnormal function of ion channels. This group of muscle diseases also comprises hyperkalemic periodic paralysis and paramyotonia congenita, both sodium-channel diseases, and myotonia congenit...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus D3S47 (probe C17), with no recombination, in a single large Irish family. Other ADRP pedigrees have shown linkage at zero recombination, linkage with recombination, and no linkage, demonstrating genetic heterogeneity. The gene encoding rh...
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::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::The late-infantile-onset forms are the most genetically heterogeneous group among the autosomal recessively inherited neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). The Turkish variant was initially considered to be a distinct genetic entity, with clinical presentation similar to that of other...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/518902
更新日期:2007-07-01 00:00:00
abstract::The estimate of heterozygosity and proportion of polymorphic loci for 33 red blood cell loci has been updated by the elimination of some loci of questionable status and the addition of data on 33 loci. The new figures for heterozygosity and proportion of polymorphic loci, .105 and .283, respectively, are based on 60 r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00