Abstract:
:In type I familial amyloid polyneuropathy (FAP) caused by a variant Met30-transthyretin (TTR), genetic anticipation has been reported. To determine whether anticipation of the disease is a true biological phenomenon or the result of ascertainment bias, we compared age at onset of the affected child with that of the affected parent in 68 parent-child pairs (including data on assumed age at onset and on asymptomatic obligate heterozygotes and parents at obligate 50% risk) in 15 families. Excluding the parent-child pairs involving the proband and "bilineal pairs", onset occurred earlier in the child than in the transmitting parent in 60 out of 68 "unilineal pairs". After correction for ascertainment bias resulting from incomplete penetrance and reduced biological fitness in early onset patients, the number of anticipation pairs (60 pairs) was still significantly larger than that of non-anticipation pairs (29.7 pairs) (p < 0.05). When the children were sons, the difference in age at onset was significantly greater in the mother-son pairs than in the father-son pairs (p = 0.023). Although not all ascertainment biases could be eliminated, these data show strong evidence that anticipation in the transmission of Met30-TTR FAP is a true biological phenomenon.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Yamamoto K,Ikeda S,Hanyu N,Takeda S,Yanagisawa Ndoi
10.1136/jmg.35.1.23subject
Has Abstractpub_date
1998-01-01 00:00:00pages
23-30issue
1eissn
0022-2593issn
1468-6244journal_volume
35pub_type
杂志文章abstract::In the majority of patients, familial hypercholesterolaemia (FH) is caused by different mutations affecting the well defined low density lipoprotein receptor (LDLR) gene. However, 3% of patients in Munich with a clinical diagnosis of FH have a particular mutation in the apolipoprotein B gene causing familial defective...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.28.12.865
更新日期:1991-12-01 00:00:00
abstract::The chemical and physical properties of haemoglobin S derived from homozygotes for this haemoglobin in Sicily were examined, as well as some erythrocytic characteristics. Sicilian Hb S was identical to that found in USA black patients in electrophoretic mobility on both starch and citrate agar media, solubility, mecha...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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abstract::Four studies reported an increasing incidence of pyloric stenosis during the late 1970s from geographically diverse areas of the United Kingdom. It was suggested that the increased incidence might be related to changes in infant feeding practices. We used data from the Metropolitan Atlanta Congenital Defects Program, ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.24.8.482
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abstract::Relatively few point mutations have been found in the dystrophin gene and of these only two have been associated with mosaicism. A single base insertion has been identified and quantified in a mother of two sons affected with Duchenne muscular dystrophy. It has been determined that she is a somatic mosaic with the mut...
journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.11.924
更新日期:1998-11-01 00:00:00
abstract::The fragile X syndrome is a common cause of mental impairment. In view of the low reproductive fitness of affected males, the high incidence of the syndrome has been suggested to be the result of a high rate of new mutations occurring exclusively in the male germline. Extensive family studies, however, have failed to ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
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更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. METHODS:A literature search revealed 690 different phenylalanine hydroxylase genotypes in 30...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2014-102621
更新日期:2015-03-01 00:00:00
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.053942
更新日期:2008-01-01 00:00:00
abstract::The features of a child with osteogenesis imperfecta type III (OI III) resulting from the heterozygous substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen were studied. He was born at term with the clinical features of severe OI, including deep grey-blue sclerae. He had severe ost...
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pub_type: 杂志文章
doi:10.1136/jmg.33.3.193
更新日期:1996-03-01 00:00:00
abstract:BACKGROUND:Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH f...
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pub_type: 杂志文章
doi:10.1136/jmedgenet-2019-106474
更新日期:2020-06-01 00:00:00
abstract::Autosomal dominant sacral agenesis is characterised by a partial agenesis of the sacrum typically involving sacral vertebrae S2-S5 only. Associated features include anorectal malformation, a presacral mass, and urogenital malformation. Together, these features have been defined as the Currarino syndrome. Recently, HLX...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.37.8.561
更新日期:2000-08-01 00:00:00
abstract::Despite increased expenditure, productivity of the pharmaceutical industry has decreased and currently 90% of developed molecules entering phase II and phase III clinical trials fail to gain regulatory approval. Most of these failures are due to lack of therapeutic efficacy rather than lack of safety, suggesting that ...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmedgenet-2014-102438
更新日期:2015-02-01 00:00:00
abstract::An infant with congenital chondrodysplasia punctata with a secondary deformation of umbilical cord hernia is reported. The paper discusses deformation syndromes as anomalies due to unusual mechanical or intrinsic factors. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.23.1.84
更新日期:1986-02-01 00:00:00
abstract::The occurrence in a family of an isolated case of an autosomal dominant disorder with reduced penetrance presents a difficult problem in genetic counselling. It is shown that in such a situation the risk of recurrence in subsequent offspring is given by: (formula; see text) where P is the penetrance (0 less than P les...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.23.4.316
更新日期:1986-08-01 00:00:00
abstract::A brother and two sisters of remotely consanguineous parents had congenital laryngeal abductor paralysis and moderate mental retardation. In the two older sibs, mental deficiency could have resulted from birth asphyxia, but the youngest girl was already microcephalic at birth and had no apparent asphyxia. The mother, ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.27.11.715
更新日期:1990-11-01 00:00:00
abstract::Fragile X syndrome, the main cause of inherited mental retardation, is caused by transcriptional silencing of the fragile X mental retardation gene, FMR1. Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism. The core aim of this rev...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.2008.064667
更新日期:2009-09-01 00:00:00
abstract::Germline mutations in highly penetrant autosomal dominant genes explain about 5% of all breast cancer, and heritable mutations in the BRCA1 breast and ovarian cancer susceptibility gene account for 2-3% of breast cancer in the general population. Nevertheless, the presence of such mutations is highly predictive of dis...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.35.2.116
更新日期:1998-02-01 00:00:00
abstract::Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single s...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.34.6.489
更新日期:1997-06-01 00:00:00
abstract::We describe the clinical and cytogenetic findings of two patients with deletions of the long arm of chromosome 2. One has an interstitial deletion identical to that found in a previously reported patient, although they are phenotypically dissimilar. The other patient has a terminal deletion, the first such deletion re...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.20.3.199
更新日期:1983-06-01 00:00:00
abstract::Having identified teratogenic factors, primary prevention of congenital defects is possible by the implementation of specific measures in pregnant women or those planning pregnancy. Our current understanding of the epigenetic processes acting during reproductive events raises new possibilities to prevent both heritabl...
journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
doi:10.1136/jmg.2009.070466
更新日期:2010-02-01 00:00:00
abstract::We have performed linkage analysis in seven Italian families, in which mild osteogenesis imperfecta (OI) segregated as a dominant trait, by means of six DNA restriction fragment length polymorphisms (RFLPs) of type I collagen genes. OI type I was linked to the alpha 1(I) gene (COL1A1) in two families, and to the alpha...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.27.6.367
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control th...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmedgenet-2016-103956
更新日期:2017-01-01 00:00:00
abstract::Three sisters with gonadoblastoma and an 46,XY karyotype are presented. This observation suggests that heredity may play an important role in the genesis of the tumour. ...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.14.3.194
更新日期:1977-06-01 00:00:00
abstract::Late onset Huntington's disease is characterised by onset of symptoms after the age of 50 and is usually associated with a milder course. We have analysed the CAG trinucleotide repeat within the HD gene in 133 late onset patients from 107 extended families. The median upper allele size for the CAG repeat was 42 with a...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.30.12.991
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified. METHODS:Because Yakuts are considered as a population isolate and the disease is ra...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.2007.051979
更新日期:2007-12-01 00:00:00
abstract::A sequential silver-Giemsa (SG) procedure is presented, initially to stain the p11 and q11 euchromatic bands and subsequently the q12 heterochromatic band of the human Y chromosomes. A three sub-band division of the q11 band can be identified. The same technique differentially stains the secondary constriction of chro...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.17.6.468
更新日期:1980-12-01 00:00:00
abstract::Leprechaunism is a rare autosomal recessive disorder associated with extreme insulin resistance with paradoxical hypo-glycaemia. It is characterised by prenatal and postnatal growth retardation, reduced subcutaneous tissue, coarse features, acanthosis nigricans, enlarged genitalia, and death in the first year of life....
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.30.6.470
更新日期:1993-06-01 00:00:00
abstract::In an attempt to relate the age at onset of Huntington's disease to parental factors, the effects of parental onset-age (Po) and the age of the transmitting parent at the birth of a subsequently affected child (Pc) have been examined in a sample of cases ascertained from Victorian kindreds. There was a significant pos...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.12.1.64
更新日期:1975-03-01 00:00:00
abstract::The long-term decline in the incidence of the neural tube malformations, anencephaly and spina bifida (ASB), ended in the mid-1950's in New York State. Since that time, the rate of these birth defects has remained between 1 and 1.5/1000 births. In this low incidence population, we tested the basic tenets which support...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.15.2.101
更新日期:1978-04-01 00:00:00
abstract::A 4 year old boy is reported with tyrosinase positive hypopigmentation, mental retardation, ataxia, and myopia. Radiological investigation showed occipital cerebral atrophy, coxa valga, and generalised osteoporosis. The skin histology and electron microscopy are reported and discussed. The clinical features are simila...
journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:10.1136/jmg.24.2.118
更新日期:1987-02-01 00:00:00