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131.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
132.
C. W. Ang K. Krogfelt P. Herbrink J. Keijser W. van Pelt T. Dalby M. Kuijf B. C. Jacobs M. P. Bergman P. Schiellerup C. E. Visser 《Clinical microbiology and infection》2007,13(9):915-922
Weeks or months following Campylobacter infection, a small proportion of infected individuals develop Guillain-Barré syndrome (GBS) or reactive arthritis (ReA). Stool culture for Campylobacter is often negative in these patients, and serology is therefore the method of choice for diagnosing a recent infection with Campylobacter. This study developed a capture ELISA system to detect anti-Campylobacter IgA and IgM antibodies indicative of a recent infection. The sensitivity of the assay was 82.0% in uncomplicated Campylobacter enteritis patients, 96.2% in GBS patients who were culture-positive for Campylobacter, and 93.1% in culture-positive ReA patients, with a specificity of 93.0%. The assay allows identification of Campylobacter infection in patients with post-infectious neurological and rheumatological complications. 相似文献
133.
A standard atlas space with stereotaxic co-ordinates for the postnatal day 0 (P0) C57BL/6J mouse brain was constructed from
the average of eight individual co-registered MR image volumes. Accuracy of registration and morphometric variations in structures
between subjects were analyzed statistically. We also applied this atlas coordinate system to data acquired using different
imaging protocols as well as to a high-resolution histological atlas obtained from separate animals. Mapping accuracy in the
atlas space was examined to determine the applicability of this atlas framework. The results show that the atlas space defined
here provides a stable framework for image registration for P0 normal mouse brains. With an appropriate feature-based co-registration
strategy, the probability atlas can also provide an accurate anatomical map for images acquired using invasive imaging methods.
The atlas templates and the probability map of the anatomical labels are available at . 相似文献
134.
135.
Baer L Jacobs DG Meszler-Reizes J Blais M Fava M Kessler R Magruder K Murphy J Kopans B Cukor P Leahy L O'Laughlen J 《Psychotherapy and psychosomatics》2000,69(1):35-41
BACKGROUND: The present study was designed to develop a briefer screening scale of approximately 10 items which maintained the validity of the Zung Self-Rating Depression Scale in a sample similar to that attending National Depression Screening Day (NDSD), as well as a more general audience. METHODS: We first administered 70 items from a variety of existing rating scales to 40 subjects who answered an ad for depressed subjects and 55 who answered an ad for non-depressed subjects, all of whose diagnoses were confirmed by the Structured Clinical Interview for DSM-IV (SCID). Based on the correlation between each item and the diagnostic criterion, we reduced the number of items to 17 which we then administered to another 45 subjects who answered an ad similar to that used for NDSD and also underwent a SCID interview. Based on these results, we arrived at the final 10-item Harvard Department of Psychiatry/NDSD scale (HANDS) with the assistance of the item-response theory. The items are scored for frequency of occurrence of each symptom over the past 2 weeks. Total scores range from 0 to 30. RESULTS: The 10-item scale (HANDS) has good internal consistency and validity: a cutpoint score of 9 or greater gave sensitivity of at least 95% in both studies. Although specificity was lower for all scales in the self-selected population, the HANDS performed at least as well as the 20-item Zung Scale, the 21-item Beck Depression Inventory-II and the 15-item Hopkins Symptom Depression Checklist. CONCLUSION: The 10-item HANDS performs as well as other widely used longer self-report scales and has the advantage of briefer administration time. 相似文献
136.
The fragile (X) syndrome: the mutation problem 总被引:2,自引:0,他引:2
In an attempt to understand the nature of the mutational event leading to the fra(X) syndrome, we have searched for sporadic cases in 3 populations: affected males, affected females, and non-affected transmitting females. In all 3 populations there was a dearth of isolated cases, and the reasons for this are discussed. 相似文献
137.
Patricia A. Jacobs Janice S. Matsuura Martha Mayer Irene M. Newlands 《Clinical genetics》1978,13(1):37-60
A cytogenetic survey of 475 patients in an institution for the mentally retarded is reported. The chromosomes of all patients were studied using both a non-banding and a G-banding technique in order to estimate the relative efficiency of the two technique in detecting structural rearrangements of the chromosomes. A total of 57 patients was found to have a chromosome abnormality, including five with a balanced structural rearrangement. The contribution of chromosome aberrations to the etiology of mental retardation is discussed with special emphasis on the contribution of balanced structural rearrangements. 相似文献
138.
Michaelsen SM Jacobs S Roby-Brami A Levin MF 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2004,157(2):162-173
Previous studies have shown that patients with arm and hand paresis following stroke recruit an additional degree of freedom (the trunk) to transport the hand during reaching and use alternative strategies for grasping. The few studies of grasping parameters of the impaired hand have been case studies mainly focusing on describing grasping in the presence of particular impairments such as hemi-neglect or optic ataxia and have not focussed on the role of the trunk in prehension. We hypothesized that the trunk movement not only ensures the transport of the hand to the object, but it also assists in orienting the hand for grasping when distal deficits are present. Nineteen patients with chronic hemiparesis and seven healthy subjects participated in the study. Patients had sustained a stroke of non-traumatic origin 6–82 months previously (31±22 months) and had mild or moderate to severe arm paresis. Using a whole hand grasp, subjects reached and grasped a cylinder (35 mm) that was placed sagittally (T1) or at a 45° angle to the sagittal midline in the ipsilateral workspace (T2), both at about 90% arms length (10 trials per target). Eight infrared emitting diodes were placed on bony landmarks of the hand, arm and trunk and kinematic data were recorded by an optical motion analysis system (Optotrak) for 2–5 s at 120 Hz. Hand position and orientation were recorded by a Fastrack Polhemus system. Our results show that during goal-directed prehension tasks, individuals with hemiparesis oriented the hand more frontally for grasping and used more trunk anterior displacement or rotation to transport the hand to the target compared to healthy subjects. Despite these changes, the major characteristics of reaching and grasping such as grip aperture size, temporal coordination between hand transport and aperture formation and the relative timing of grip aperture were largely preserved. For patients with more severe distal impairments, the amount of trunk displacement was also correlated with a more frontal hand orientation for grasping. Furthermore, in healthy subjects and patients without distal impairments, the trunk movement was mostly related to proximal arm movements while in those with distal impairments, trunk movement was related to both proximal and distal arm movements. Data support the hypothesis that the trunk movement is used to assist both arm transport and hand orientation for grasping when distal deficits are present. 相似文献
139.
A J Cohen F P Li S Berg D J Marchetto S Tsai S C Jacobs R S Brown 《The New England journal of medicine》1979,301(11):592-595
140.