Abstract:
:The molecular genetics of GM1 beta-galactosidase is reviewed. This enzyme exists in two forms, A and B. Form A is monomeric with a molecular weight of 72,000 and appears to be coded by a single autosomal locus. Form B is polymeric and cross-reacts with anti-A antibodies; it is coded wholly or in part by the same locus that codes for A. The simultaneous loss of A and B in GM1 gangliosidosis is explained. None of the other beta-galactosidases, including neutral beta-galactosidase, ceramide lactoside beta-galactosidase or cerebroside beta-galactosidase cross-react with anti-A antibodies, demonstrating that they are coded by loci separate from A. GM1 beta-galactosidase A is heterocatalytic, cleaving beta-D-galactose from ganglioside GM1, lactose, N-acetyllactosamine, and galactose-containing glycoproteins such as asialofetuin, red cell stromal glycoproteins and keratan sulfate. The pleotropic effects of a single mutation affecting the locus for beta-galactosidase A can be explained by a one gene:one polypeptide:many substrates model. Phenotypic variability among beta-galactosidase A mutants may result from better residual activity of the mutant enzyme for one substrate than for another. Patients with normal intelligence and severe bony deformities, who are homozygous for a mutation affecting the enzyme, illustrate this point. Thus far all human mutants for GM1 beta-galactosidase studied are structural mutants, synthesizing nearly normal quantities of mutant enzyme; one is a proven Km mutant, the others are very likely so.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
O'Brien JSsubject
Has Abstractpub_date
1975-11-01 00:00:00pages
303-13issue
5eissn
0009-9163issn
1399-0004journal_volume
8pub_type
杂志文章,评审abstract::Mutations in the CDH23 gene are known to be responsible for both Usher syndrome type ID (USH1D) and non-syndromic hearing loss (DFNB12), and the molecular confirmation of the CDH23 gene has become important in the diagnosis of these conditions. The present study was performed to find whether the CDH23 mutations are al...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2007.00833.x
更新日期:2007-10-01 00:00:00
abstract::The dentin sialophosphoprotein (DSPP) gene encodes the most abundant non-collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the DSPP gene have been solely related to non-syndromic form of hereditary dentin ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01483.x
更新日期:2011-04-01 00:00:00
abstract::Clinical, cytogenetic, and immunological data of a 5-year-old Japanese girl with Bloom's syndrome are described. Growth deficiency, photosensitivity, and a very mild facial telangiectatic erythema were present. Cytological studies revealed chromosomal aberrations and the characteristic high frequency in sister chromat...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1980.tb00123.x
更新日期:1980-02-01 00:00:00
abstract::We have detected a novel mutation in the adrenoleukodystrophy (ALD) gene in skin fibroblasts in primary culture derived from a patient suffering from the adrenocortical insufficiency-only-phenotype of ALD. This nonsense mutation (C2400T/Q672X) is the only mutation reported to date affecting exon 10. It leads to a tran...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb02600.x
更新日期:1998-06-01 00:00:00
abstract::In order to evaluate the involvement of the peripheral autonomic nervous system in the pathogenesis of type 1 familial amyloid polyneuropathy, the urinary excretion rates of catecholamines and serum dopamine-beta-hydroxylase (DB/) activity were examined in 22 patients at various clinical stages. Changes in both indice...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1979.tb00860.x
更新日期:1979-08-01 00:00:00
abstract::Complex genetic diseases are often common: in most common diseases liability is influenced by genetic variation. The ways in which this variation is analyzed are discussed using diabetes, affective disorders and schizophrenia as examples. Molecular biology has opened new paths for a more incisive analysis of genetic h...
journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/j.1399-0004.1989.tb03218.x
更新日期:1989-11-01 00:00:00
abstract::The concurrence of a short arm isochromosome and a translocation of the entire long arm of the same chromosome to a telomere of another chromosome, implying trisomy for 4p, 5p, 7p, 9p, 10p or 12p, has been described in 13 patients. We have now used fluorescence in situ hybrization (FISH) to better characterize one of ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.1999.550209.x
更新日期:1999-02-01 00:00:00
abstract::Patients with restrictive cardiomyopathy (RC) have impaired diastolic function, but intact systolic function until later stages of the disease, ultimately leading to heart failure. Primary RC is often sporadic, but also may be inherited in an autosomal dominant fashion, particularly the idiopathic forms. Recently ther...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2001.590406.x
更新日期:2001-04-01 00:00:00
abstract::A girl in whom a ring chromosome 13 was found, presented with microcephaly, mental retardation and multiple minor malformations. She was born after a full term pregnancy, small for date and with a small head circumference. She underwent craniotomy at the age of 18 months because of premature closure of the metopic sut...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb00320.x
更新日期:1975-03-01 00:00:00
abstract::The effect of folic acid intake on the frequency of fragile X positive cells and some behavioural characteristics were evaluated in 5 boys and 4 adult males with the fragile X syndrome. The expression of fragile X was nullified in 6 and decreased in 3 of the 9 patients. Behavioural and motor ability were considered to...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1985.tb00232.x
更新日期:1985-05-01 00:00:00
abstract::Congenital aniridia is due to deletions and point mutations in the PAX6 gene. We describe here a case of a mother and her two sons with a syndrome comprising congenital aniridia, ptosis, and slight mental retardation. The sons also show behavioral changes. The possibility of deletion around the PAX6 locus was excluded...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2001.600210.x
更新日期:2001-08-01 00:00:00
abstract::Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal alpha-galactosidase A [EC 3.2.1.22]. The molecular diagnosis of Fabry disease is important for genotype/phenotype correlation, pre-natal or early diagnosis, and detection of carrier status. Although more than 200 genotypes of the alpha-galac...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1034/j.1399-0004.2003.00050.x
更新日期:2003-03-01 00:00:00
abstract::Hereditary spastic paraplegia (HSP) is rarely inherited in an X-linked recessive mode in pure and complicated forms. Recently, molecular linkage studies have suggested that these variant X-linked HSP conditions result from locus heterogeneity. In this paper we report on the clinical and linkage analysis of a kindred w...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1989.tb02915.x
更新日期:1989-02-01 00:00:00
abstract::Disorders of sex development (DSD) are rare disorders in which there is discordance between chromosomal, gonadal, and phenotypic sex. Only a minority of patients clinically diagnosed with DSD obtains a molecular diagnosis, leaving a large gap in our understanding of the prevalence, management, and outcomes in affected...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2012.01879.x
更新日期:2013-01-01 00:00:00
abstract::Array comparative genomic hybridization (aCGH) has progressively replaced conventional karyotype in the diagnostic strategy of intellectual disability (ID) and congenital malformations. This technique increases not only the diagnostic rate but also the possibility of finding unexpected variants unrelated to the indica...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12421
更新日期:2015-05-01 00:00:00
abstract::Linkage analysis has been performed on a large South African family of British origin in which 39 persons in 6 generations had early onset Type I autosomal dominant retinitis pigmentosa (ADRP). Tight linkage was excluded between the disease and the D3S47 locus on chromosome 3. This finding is further evidence for gene...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1992.tb03406.x
更新日期:1992-06-01 00:00:00
abstract::A photoanthropometric method, which enables an objective description of facial structures, was used to better delineate the craniofacial characteristics of 29 individuals with Williams syndrome (WS; 18 males and 11 females) between the ages of 0 to 10 years, with an average age of 4.0 years. Facial parameters were mea...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1997.tb02495.x
更新日期:1997-06-01 00:00:00
abstract::A case of mosaic trisomy 8 is described and the accuracy of flask culture and in situ culture techniques in detecting chromosomal mosaicism in tissues discussed. The advantages of the in situ method are illustrated and the importance of mixed colonies in defining mosaicism highlighted. The implications for prenatal di...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1984.tb01989.x
更新日期:1984-03-01 00:00:00
abstract::Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge mea...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12618
更新日期:2016-02-01 00:00:00
abstract::The locus DXS255 was studied using the probe M27 beta in ten probands with Rett syndrome and in eight of their families. No evidence of uniparental disomy of the X chromosome was detected, as all informative probands had inherited an allele from each of their parents. Differential methylation of a CCGG site within the...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1993.tb03889.x
更新日期:1993-11-01 00:00:00
abstract::The aim of this work was to determine the impact of parental consanguinity on congenital malformations in a mixed urban and rural Arab community in Jerusalem, Israel. Arab mothers admitted to four hospitals in west Jerusalem were interviewed after delivery. Demographic and obstetric data were recorded. Neonatal data w...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.0009-9163.2004.00264.x
更新日期:2004-07-01 00:00:00
abstract::Biochemical data are presented of a 29-year-old male, who shows progressive psychomotor retardation and a beta-galactosidase deficiency in leucocytes and cultured skin fibroblasts. Somatic cell hybridization studies show that this variant of GM1-gangliosidosis is based on a different gene mutation than is present in t...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb02272.x
更新日期:1976-04-01 00:00:00
abstract::Single cells were sorted from cultured fibroblasts of five carriers of Fabry's disease using a cell sorter (FACS II). The alpha-galactosidase A activity in the single fibroblasts was assayed in nanoliter droplets with the help of quantitative microfluorimetric techniques. Two populations of fibroblasts were present in...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1983.tb01874.x
更新日期:1983-04-01 00:00:00
abstract::Autosomal dominant hereditary polycystic kidney disease (ADPKD) is the most common inherited kidney disease that causes end-stage renal disease and kidney failure. Preimplantation genetic testing for monogenic (PGT-M) can effectively prevent the transmission of genetic diseases from parents to the offspring before pre...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.13871
更新日期:2021-02-01 00:00:00
abstract::Methods are presented to estimate relative fitness of carriers as a function of fertility, survival, are generation time in pedigrees under incomplete ascertainment. A large sample of diverse chromosomal aberrations reveals significant effects on all three parameters, giving a relative fitness of .769 +/- .039. There ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1975.tb01489.x
更新日期:1975-09-01 00:00:00
abstract::The physician-patient relationship was governed for centuries by the ethical principle of beneficence and the physician's dedication to the principle of doing no harm. This structure shifted, however, to the principle of personal autonomy as medical and surgical knowledge expanded and patients, rather than physicians,...
journal_title:Clinical genetics
pub_type: 历史文章,杂志文章,评审
doi:10.1111/j.1399-0004.2004.00324.x
更新日期:2005-01-01 00:00:00
abstract::We describe the neurological evaluation and MRI analysis of 30 patients, belonging to 16 families with Usher syndrome (US) type I and type II (US1 and US2). In addition to the classic visual and audiological abnormalities seen in these patients, we observed abnormal gait in 88.9% of US1 and in 66.7% of US2 patients an...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1996.tb02366.x
更新日期:1996-09-01 00:00:00
abstract::Mutations in the myelin protein zero (MPZ) gene are one of the frequent causes of Charcot-Marie-Tooth (CMT) hereditary neuropathies. Because the mutation rate of MPZ gene is rather high and some mutations are reported as polymorphisms, the proper clinical, electrophysiological examination and the segregation of the ne...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.2010.01423.x
更新日期:2010-07-01 00:00:00
abstract::Marinesco-Sjøgren syndrome and hypergonadotropic hypogonadism were observed in two kindreds, and they were found to occur togetherin 9 out of 10 affected individuals. The last patient had Marinesco-Sjøgren syndrome without manifestations of hypogonadism, and similar findings were observed in two affected sisters from ...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1977.tb01279.x
更新日期:1977-01-01 00:00:00
abstract::In a study of xanthomatosis in the county of Ostfold, Norway (approximately 220,000 inhabitants), it was found that 20% (37 out of 185) of the probands belonges to seven large kindreds where xanthomatosis and hyper-beta-lipoproteinaemia segregated. Almost complete ascertainment (99%) of living subjects in the sibships...
journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb01554.x
更新日期:1976-01-01 00:00:00