Localization of a gene for Möbius syndrome to chromosome 3q by linkage analysis in a Dutch family

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Incidence and survival of retinoblastoma in the Netherlands: a register based study 1862-1995

AIM—The aim of this study was to determine the (time trends in) incidence and survival of hereditary (familial and sporadic) and non-hereditary retinoblastoma for male and female patients born in the Netherlands between 1862 and 1995.
METHOD—The national retinoblastoma register was updated and now consists of 955 patients. The missing dates of death were obtained from the municipal registers and the Central Bureau of Genealogy in The Hague. Mortality was compared with the Dutch vital statistics.
RESULTS—From 1862 to 1995 no significant differences in incidence for retinoblastoma were found in the hereditary subgroups. Further, no significant differences between males and females were found, both overall and in the hereditary subgroups. The average incidence of retinoblastoma increased untill 1944, probably due to incompleteness of the register, and stabilised after 1945 (1 per 17 000 live births). From 1900 to 1995 the standardised mortality ratio increased for hereditary retinoblastoma patients from 2.9 to 9.0 and decreased for non-hereditary retinoblastoma patients from 1.9 to 1.0.
CONCLUSION—Although survival for retinoblastoma was significantly better after 1945 than before, in comparison with the Dutch population the mortality between 1900 and 1990 increased for the hereditary and decreased for the non-hereditary retinoblastoma patients.


Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36

Polydactyly is the most frequently observed congenital hand malformation with a prevalence between 5 and 19 per 10 000 live births. It can occur as an isolated disorder, in association with other hand/foot malformations, or as a part of a syndrome, and is usually inherited as an autosomal dominant trait. According to its anatomical location, polydactyly can be generally subdivided into pre- and postaxial forms. Recently, a gene responsible for preaxial polydactyly types II and III, as well as complex polysyndactyly, has been localised to chromosome 7q36.
In order to facilitate the search for the underlying genetic defect, we ascertained 12 additional families of different ethnic origin affected with preaxial polydactyly. Eleven of the kindreds investigated could be linked to chromosome 7q36, enabling us to refine the critical region for the preaxial polydactyly gene to a region of 1.9 cM. Our findings also indicate that radial and tibial dysplasia/aplasia can be associated with preaxial polydactyly on chromosome 7q36.
Combining our results with other studies suggests that all non-syndromic preaxial polydactylies associated with triphalangism of the thumb are caused by a single genetic locus, but that there is genetic heterogeneity for preaxial polydactyly associated with duplications of biphalangeal thumbs. Comparison of the phenotypic and genetic findings of different forms of preaxial polydactyly is an important step in analysing and understanding the aetiology and pathogenesis of these limb malformations.


Keywords: preaxial polydactyly; chromosome 7q36; localisatio

The radiation tolerance of specific optical fibres exposed to 650 kGy(Si) of ionizing radiation

The LHC upgrade will extensively increase the area of silicon detectors used in the ATLAS experiment and require substantial changes to the readout system of both the ATLAS and CMS experiments. The two experiments are expected to use optical systems for part of the data and control paths which must withstand levels of radiation equivalent to a dose of approximately 400 kGy(Si) at 30 cm from the collision region (including a safety factor of 1.5). As part of the search for acceptably radiation hard optical fibres, four Graded Index multimode (GRIN) optical fibres and one single-mode (SM) fibre were tested to 650 kGy(Si) equivalent dose. One of the GRIN fibres was also tested at 5 different dose rates, in order to understand the dose rate effects. These tests have validated the radiation tolerance of a single-mode fibre and two multimode fibres for use at the SLHC for warm operation. Some interesting features of the time dependence of the fibre radiation damage and future plans are discussed. © 2009 IOP Publishing Ltd and SISSA

Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation

© 2002 Elsevier Science (USA). All rights reserved.The differential regulation of cAMP levels within the oocyte and somatic (cumulus) cell compartments of the bovine follicle, and the subsequent regulation of oocyte meiotic maturation was examined through specific cell-type localisation of phosphodiesterases (PDEs). Selective PDE inhibitors were used to modulate cAMP levels in each of the two follicular compartments and to examine their effects on oocyte meiotic maturation. Ovaries were obtained from an abattoir and cumulus-oocyte complexes (COC) were aspirated from antral follicles into culture medium supplemented with 4 mg/ml BSA and 2mM 3-isobutyl-1-methylxanthine (IBMX). COC, denuded oocytes (DO), or mural granulosa cells (MGC) were cultured either with or without forskolin or FSH, in the presence of specific PDE inhibitors; either milrinone (PDE3 inhibitor), cilostamide (PDE3 inhibitor), or rolipram (PDE4 inhibitor). COC/DO cultures were assessed for meiotic progression and cAMP content, and MGC for cAMP production. The type 3 PDE inhibitor, but not the type 4, prevented spontaneous meiotic maturation and elevated intraoocyte cAMP in cultured denuded oocytes. In contrast, the type 4 PDE inhibitor had no effect on the oocyte, but elevated mural granulosa and cumulus cell cAMP production. The results of this study indicate that specific PDE subtypes are differentially localised within the two compartments of the bovine follicle—the type 3 PDE in the oocyte and the type 4 PDE in the granulosa cells. In addition, oocyte cAMP levels are primarily regulated in bovine oocytes by its degradation by PDE, whereas granulosa cell cAMP levels are controlled mainly by active adenylate cyclase, with both sources able to participate in oocyte meiotic regulation

Paracentric inversion inv(11) (q21q23) in the Netherlands

We report the result of investigations from 20 families with 72 carriers of the paracentric inversion inv(11)(q21q23) in the Netherlands. There is no increase in the rate of spontaneous abortions among carriers of the inversion or their partners. Also, so far, there are no children with recombinant chromosomes arising from the inversion. It is doubtful whether prenatal diagnosis would be helpful to carriers of this inversion. The results of the genealogy study and geographical distribution are discussed; it is suggested that all the families have arisen from a single mutation

Irradiation Studies of Multimode Fibres for use in ATLAS Front-end Links

The radiation tolerance of three multimode optical fibres has been investigatedto establish their suitability for use in the front-end data links of the ATLAS experiment. Both gamma and neutron irradiation studies are reported. A step-index fibre with a pure silica core showed an induced attenuation of $\sim$0.05~dB/mat 330~kGy(Si) and 1$\times$10$^{15}$~n(1~MeV~Si)/cm$^{2}$ and is suitablefor use with the inner detector links which operate at 40-80~Mb/s. A graded-indexfibre with a predominantly germanium doped core exhibits an induced attenuation of $\sim$0.1~dB/mat 800~Gy(Si) and 2$\times$10$^{13}$~n(1~MeV~Si)/cm$^{2}$ and is suitable for the calorimeterlinks which operate at 1.6~Gb/s. Measurements of the dose rate dependence of the induced attenuation indicate that the attenuation in ATLAS will be lower