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11.
Edward?J?HolloxEmail author Jane?Davies Uta?Griesenbach Juliana?Burgess Eric?WFW?Alton John?AL?Armour 《Journal of negative results in biomedicine》2005,4(1):9
Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in
lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in
copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic
fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with
CF. No significant association was found. 相似文献
12.
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1) 总被引:10,自引:1,他引:10
Rousseau F; el Ghouzzi V; Delezoide AL; Legeai-Mallet L; Le Merrer M; Munnich A; Bonaventure J 《Human molecular genetics》1996,5(4):509-512
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
相似文献
13.
Dr. U. Cordes B. Braun M. Georgi F. Kümmerle V. Lenner E. Magin T. Philipp J. Beyer 《Journal of molecular medicine (Berlin, Germany)》1979,57(22):1209-1215
Zusammenfassung Bei sechs Patienten mit adrenalem Phäochromocytom erfolgte die Lokalisationsdiagnostik durch Ultraschalluntersuchung, Phlebographie der Nebennieren und selektiver Katecholaminbestimmung im Blut der Vena cava sowie der Nebennierenvenen. Durch die selektive Katecholaminbestimmung konnten alle Phäochromocytome lokalisiert werden, durch die Ultraschalluntersuchung fünf, durch die Phlebographie vier. Ein Phäochromocytom von 1,5 g Gewicht, das nur durch die selektive Katecholaminbe-stimmung, nicht aber durch Ultraschall oder Phlebographie lokalisiert wurde, konnte computertomographisch dargestellt werden.Um Fehldiagnosen bei der selektiven Katecholaminbestimmung zu vermeiden, darf vor der Blutentnahme aus den Nebennierenvenen kein Röntgenkontrastmittel injiziert werden, da dies zu einer erheblichen Adrenalin- oder Noradrenalinfreisetzung aus dem Nebennierenmark führen kann. 相似文献
14.
A molecular oscillator that controls the expression of cyclic genes such as lunatic fringe (Lfng) in the presomitic mesoderm has been shown to be coupled with somite formation in vertebrate embryos. To address the functional significance of oscillating Lfng expression, we have generated transgenic mice expressing Lfng constitutively in the presomitic mesoderm in addition to the intrinsic cyclic Lfng activity. These transgenic lines displayed defects of somite patterning and vertebral organization that were very similar to those of Lfng null mutants. Furthermore, constitutive expression of exogenous Lfng did not compensate for the complete loss of cyclic endogenous Lfng activity. Noncyclic exogenous Lfng expression did not abolish cyclic expression of endogenous Lfng in the posterior presomitic mesoderm (psm) but affected its expression pattern in the anterior psm. Similarly, dynamic expression of Hes7 was not abolished but abnormal expression patterns were obtained. Our data are consistent with a model in which alternations of Lfng activity between ON and OFF states in the presomitic mesoderm prior to somite segmentation are critical for proper somite patterning, and suggest that Notch signaling might not be the only determinant of cyclic gene expression in the presomitic mesoderm of mouse embryos. 相似文献
15.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
16.
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19.
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
20.
Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1 总被引:10,自引:0,他引:10
Lemmens I; Van de Ven WJ; Kas K; Zhang CX; Giraud S; Wautot V; Buisson N; De Witte K; Salandre J; Lenoir G; Pugeat M; Calender A; Parente F; Quincey D; Gaudray P; De Wit MJ; Lips CJ; Hoppener JW; Khodaei S; Grant AL; Weber G; Kytola S; Teh BT; Farnebo F; Thakker RV 《Human molecular genetics》1997,6(7):1177-1183