A hot Jupiter orbiting a 2-million-year-old solar-mass T Tauri star.

Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star. It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks, or later, once multiple planets are formed and interact. Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars, whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planet­disk interactions.

ESHRE PGD Consortium data collection XIV-XV: cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013.

STUDY QUESTION: How does the data collection XIV-XV of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium compare with the cumulative data for data collections I-XIII? SUMMARY ANSWER: The 14th and 15th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the increased application of array technology at the cost of FISH testing in PGS cycles and in PGD cycles for chromosomal abnormalities. WHAT IS KNOWN ALREADY: Since 1999, the PGD Consortium has collected, analysed and published 13 previous data sets and an overview of the first 10 years of data collections. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a FileMaker Pro database (versions 5-12). Separate predesigned FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar years 2011 and 2012 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2013). PARTICIPANTS/MATERIALS, SETTINGS, METHOD: Data were submitted by 71 centres (full PGD Consortium members). Records with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XIV-XV, 71 centres reported data for 11 637 cycles with oocyte retrieval (OR), along with details of the follow-up on 2147 pregnancies and 1755 babies born. A total of 1953 cycles to OR were reported for chromosomal abnormalities, 144 cycles to OR for sexing for X-linked diseases, 3445 cycles to OR for monogenic diseases, 6095 cycles to OR for PGS and 38 cycles to OR for social sexing. From 2010 until 2012, the use of arrays for genetic testing increased from 4% to 20% in PGS and from 6% to 13% in PGD cycles for chromosomal abnormalities; the uptake of biopsy at the blastocyst stage (from <1% up to 7%) was only observed in cycles for structural chromosomal abnormalities, alongside the application of array comparative genomic hybridization. LIMITATIONS, REASONS FOR CAUTION: The findings apply to the 71 participating centres and may not represent worldwide trends in PGD. WIDER IMPLICATIONS OF THE FINDINGS: The annual data collections provide an important resource for data mining and for following trends in PGD/PGS practice. STUDY FUNDING/COMPETING INTEREST(S): None.

A transiting giant planet with a temperature between 250 K and 430 K.

Of the over 400 known exoplanets, there are about 70 planets that transit their central star, a situation that permits the derivation of their basic parameters and facilitates investigations of their atmospheres. Some short-period planets, including the first terrestrial exoplanet (CoRoT-7b), have been discovered using a space mission designed to find smaller and more distant planets than can be seen from the ground. Here we report transit observations of CoRoT-9b, which orbits with a period of 95.274 days on a low eccentricity of 0.11 +/- 0.04 around a solar-like star. Its periastron distance of 0.36 astronomical units is by far the largest of all transiting planets, yielding a 'temperate' photospheric temperature estimated to be between 250 and 430 K. Unlike previously known transiting planets, the present size of CoRoT-9b should not have been affected by tidal heat dissipation processes. Indeed, the planet is found to be well described by standard evolution models with an inferred interior composition consistent with that of Jupiter and Saturn.

ESHRE PGD Consortium data collection XIII: cycles from January to December 2010 with pregnancy follow-up to October 2011.

STUDY QUESTION: How do data in the 13th annual data collection (Data XIII) of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium compare with the cumulative data for collections I-XII? SUMMARY ANSWER: The 13th retrospective collection represents valuable data on PGD/PGS cycles, pregnancies and children: the main trend observed is the decrease in the routine implementation of PGS. WHAT IS KNOWN ALREADY: Since 1999, the PGD Consortium has collected, analysed and published 12 data sets and an overview of the first 10 years of data collections. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a FileMaker Pro database (versions 5-11). Separate predesigned FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2010 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2011). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were submitted by 62 centres (full PGD Consortium members). The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XIII, 62 centres reported data for 5780 cycles with oocyte retrieval (OR), along with details of the follow-up on 1503 pregnancies and 1152 babies born. A total of 1071 OR were reported for chromosomal abnormalities, 108 OR for sexing for X-linked diseases, 1574 OR for monogenic diseases, 2979 OR for preimplantation genetic screening and 48 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION: The findings apply to the 62 participating centres and may not represent worldwide trends in PGD. WIDER IMPLICATIONS OF THE FINDINGS: The annual data collections provide an important resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTERESTS: None.

ESHRE PGD Consortium data collection XII: cycles from January to December 2009 with pregnancy follow-up to October 2010.

STUDY QUESTION: How do data in the 12th annual data collection (Data XII) of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis (PGD) Consortium compare with the cumulative data for collections I-XI? SUMMARY ANSWER: Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. WHAT IS KNOWN ALREADY: The PGD Consortium has collected, analysed and published 11 previous data sets since 1997. STUDY DESIGN, SIZE, DURATION: Data were collected from each participating centre using a pre-designed FileMaker Pro database (versions 5-10). Separate FileMaker Pro files were used for the cycles, pregnancies and baby records. The study documented cycles performed during the calendar year 2009 and follow-up of the pregnancies and babies born which resulted from these cycles (until October 2010). PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were submitted by 60 centres (full PGD Consortium members), and the blank files were distributed to each PGD Consortium member centre at the end of 2008. The submitted data were thoroughly analysed to identify incomplete data entries and corrections were requested from the participating centres. Records remaining with incomplete data were excluded from the calculations. Corrections, tables and calculations were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XII, 60 centres reported data for 6160 cycles with oocyte retrieval (OR), along with details of the follow-up on 1607 pregnancies and 1238 babies born. A total of 870 OR were reported for chromosomal abnormalities, 113 OR for sexing for X-linked diseases, 1597 OR for monogenic diseases, 3551 OR for preimplantation genetic screening and 29 OR for social sexing. LIMITATIONS, REASONS FOR CAUTION: These data cannot include every PGD cycle performed annually, and only indicate the trends in PGD worldwide. WIDER IMPLICATION OF THE FINDINGS: The annual data collections provide an extremely valuable resource for data mining and for following trends in PGD practice. STUDY FUNDING/COMPETING INTEREST(S): None.

ESHRE PGD Consortium data collection XI: cycles from January to December 2008 with pregnancy follow-up to October 2009.

The 11th report of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis Consortium is presented, documenting cycles collected for the calendar year 2008 and follow-up of the pregnancies and babies born until October 2009 which resulted from these cycles. Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection XI, 53 centres have participated, reporting on 5641 cycles to oocyte retrieval (OR), along with details of the follow-up on 1418 pregnancies and 1169 babies born. A total of 774 OR were reported for chromosomal abnormalities, 96 OR for sexing for X-linked diseases, 1363 OR for monogenic diseases, 3401 OR for preimplantation genetic screening and 5 OR for social sexing. Data XI is compared with the cumulative data for data collections I-X.

ESHRE PGD consortium best practice guidelines for amplification-based PGD.

In 2005, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium published a set of Guidelines for Best Practice PGD to give information, support and guidance to potential, existing and fledgling PGD programmes. The subsequent years have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of recent advice from ESHRE on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD, as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme, i.e. Organization of a PGD centre, fluorescence in situ hybridization-based testing, Amplification-based testing and Polar Body and Embryo Biopsy for PGD/preimplantation genetic screening. Here, we have updated the sections that pertain to amplification-based PGD. Topics covered in this guideline include inclusion/exclusion criteria for amplification-based PGD testing, preclinical validation of tests, amplification-based testing methods, tubing of cells for analysis, set-up of local IVF centre and Transport PGD centres, quality control/quality assurance and diagnostic confirmation of untransferred embryos.

ESHRE PGT Consortium data collection XIX-XX: PGT analyses from 2016 to 2017†.

STUDY QUESTION: What are the trends and developments in pre-implantation genetic testing (PGT) in 2016-2017 as compared to previous years? SUMMARY ANSWER: The main trends observed in this 19th and 20th data set on PGT are that trophectoderm biopsy has become the main biopsy stage for PGT for aneuploidies (PGT-A) and that the implementation of comprehensive testing technologies is the most advanced with PGT-A. WHAT IS KNOWN ALREADY: Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 18 data sets and an overview of the first 10 years of data collections have been published. STUDY DESIGN SIZE DURATION: The data for PGT analyses performed between 1 January 2016 and 31 December 2017 with a 2-year follow-up after analysis were provided by participating centres on a voluntary basis. Data were collected using a new online platform, which is based on genetic analysis as opposed to the former cycle-based format. PARTICIPANTS/MATERIALS SETTING METHODS: Data on biopsy method, diagnostic technology and clinical outcome were submitted by 61 centres. Records with analyses for more than one PGT for monogenic/single gene defects (PGT-M) and/or PGT for chromosomal structural rearrangements (PGT-SR) indication or with inconsistent data regarding the PGT modality were excluded. All transfers performed within 2 years after the analysis were included enabling the calculation of cumulative pregnancy rates. Data analysis, calculations, figures and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: The current data collection from 2016 to 2017 covers a total of 3098 analyses for PGT-M, 1018 analyses for PGT-SR, 4033 analyses for PGT-A and 654 analyses for concurrent PGT-M/SR with PGT-A.The application of blastocyst biopsy is gradually rising for PGT-M (from 8-12% in 2013-2015 to 19% in 2016-2017), is status quo for PGT-R (from 22-36% in 2013-2015 to 30% in 2016-2017) and has become the preferential biopsy stage for PGT-A (from 23-36% in 2013-2015 to 87% in 2016-2017). For concurrent PGT-M/SR with PGT-A, biopsy was primarily performed at the blastocyst stage (93%). The use of comprehensive diagnostic technology showed a similar trend with a small increased use for PGT-M (from 9-12% in 2013-2015 to 15% in 2016-2017) and a status quo for PGT-SR (from 36-58% in 2013-2015 to 50% in 2016-2017). Comprehensive testing was the main technology for PGT-A (from 66-75% in 2013-2015 to 93% in 2016-2017) and for concurrent PGT-M/SR with PGT-A (93%). LIMITATIONS REASONS FOR CAUTION: The findings apply to the data submitted by 61 participating centres and do not represent worldwide trends in PGT. Details on the health of babies born were not provided in this manuscript. WIDER IMPLICATIONS OF THE FINDINGS: Being the largest data collection on PGT in Europe/worldwide, the data sets provide a valuable resource for following trends in PGT practice. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding and all costs are covered by ESHRE. There are no competing interests declared. TRIAL REGISTRATION NUMBER: N/A.

ESHRE PGD Consortium data collection X: cycles from January to December 2007 with pregnancy follow-up to October 2008.

The 10th report of the European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium is presented, documenting cycles collected for the calendar year 2007 and follow-up of the pregnancies and babies born until October 2008 which resulted from these cycles. Since the beginning of the data collections there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection X, 57 centres participated, reporting on 5887 cycles to oocyte retrieval (OR), along with details of the follow-up on 1516 pregnancies and 1206 babies born. A total of 729 OR were reported for chromosomal abnormalities, 110 OR for sexing for X-linked diseases, 1203 OR for monogenic diseases, 3753 OR for preimplantation genetic screening and 92 OR for social sexing. Data X is compared with the cumulative data for data collections I-IX.

ESHRE PGT Consortium data collection XVI-XVIII: cycles from 2013 to 2015.

STUDY QUESTION: What are the trends and developments in preimplantation genetic testing (PGT) in 2013-2015 as compared to previous years? SUMMARY ANSWER: The main trends observed in the retrospective data collections 2013-2015, representing valuable data on PGT activity in (mainly) Europe, are the increased application of trophectoderm biopsy at the cost of cleavage stage biopsy and the continuing expansion of comprehensive testing technology in PGT for chromosomal structural rearrangements and for aneuploidies (PGT-SR and PGT-A). WHAT IS KNOWN ALREADY: Since it was established in 1997, the ESHRE PGT Consortium has been collecting data from international PGT centres. To date, 15 data sets and an overview of the first 10 years of data collections have been published. STUDY DESIGN SIZE DURATION: Collection of (mainly) European data by the PGT Consortium for ESHRE. The data for PGT cycles performed between 1 January 2013 and 31 December 2015 were provided by participating centres on a voluntary basis. For the collection of cycle, pregnancy and baby data, separate, pre-designed MS Excel tables were used. PARTICIPANTS/MATERIALS SETTING METHODS: Data were submitted by 59, 60 and 59 centres respectively for 2013, 2014 and 2015 (full PGT Consortium members). Records with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations, figures and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE: For data collection XVI/XVII/XVIII, 59/60/59 centres reported data on 8164/9769/11 120 cycles with oocyte retrieval: 5020/6278/7155 cycles for PGT-A, 2026/2243/2661 cycles for PGT for monogenic/single gene defects, 1039/1189/1231 cycles for PGT-SR and 79/59/73 cycles for sexing for X-linked diseases. From 2013 until 2015, the uptake of biopsy at the blastocyst stage was mainly observed in cycles for PGT-A (from 23% to 36%) and PGT-SR (from 22% to 36%), alongside the increased application of comprehensive testing technology (from 66% to 75% in PGT-A and from 36% to 58% in PGT-SR). LIMITATIONS REASONS FOR CAUTION: The findings apply to the 59/60/59 participating centres and may not represent worldwide trends in PGT. Data were collected retrospectively and no details of the follow-up on PGT pregnancies and babies born were provided. WIDER IMPLICATIONS OF THE FINDINGS: Being the largest data collection on PGT worldwide, detailed information about ongoing developments in the field is provided. STUDY FUNDING/COMPETING INTERESTS: The study has no external funding and all costs are covered by ESHRE. There are no competing interests declared. TRIAL REGISTRATION NUMBER: N/A.

ESHRE PGD Consortium data collection IX: cycles from January to December 2006 with pregnancy follow-up to October 2007.

The ninth report of the European Society of Human Reproduction and Embryology Preimplantation Genetic Diagnosis Consortium is presented documenting cycles collected for the calendar year 2006 and follow-up of the pregnancies and babies born until October 2007, which resulted from these cycles. Since the beginning of the data collections there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection IX, 57 centres have participated, reporting on 5858 cycles to oocyte retrieval (OR), along with details of the follow-up on 1437 pregnancies and 1206 babies born. Eight hundred and twelve ORs were reported for chromosomal abnormalities, 133 ORs for sexing for X-linked diseases, 931 ORs for monogenic diseases, 3900 ORs for preimplantation genetic screening and 82 ORs for social sexing. Data IX are compared with the cumulative data for data collections I-VIII.

ESHRE PGD Consortium data collection VIII: cycles from January to December 2005 with pregnancy follow-up to October 2006.

The eighth report of the European Society of Human Reproduction and Embryology PGD Consortium is presented documenting cycles collected for the calendar year 2005 and follow-up of the pregnancies and babies born until October 2006 which resulted from these cycles. For the first time, the delivery rates for each indication are presented and also the pregnancy rates for each centre are reported anonymously. Since the first data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection VIII, 39 centres have participated, reporting on 3488 cycles to oocyte retrieval (OR), along with details of the follow-up on 845 pregnancies and 670 babies born. Five hundred and twenty OR were reported for chromosomal abnormalities, 108 OR for sexing for X-linked diseases, 500 OR for monogenic diseases, 2275 OR for preimplantation genetic screening and 85 OR for social sexing. Data VIII is compared with the cumulative data for data collections I-VII.

ESHRE PGD consortium data collection VII: cycles from January to December 2004 with pregnancy follow-up to October 2005.

The seventh report of the ESHRE PGD Consortium is presented documenting cycles collected for the calendar year 2004 and follow-up of the pregnancies and babies born subsequent to these cycles up to October 2005. Since the beginning of the data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported. For data collection VII, 45 centres have participated, reporting on 3358 cycles to oocyte retrieval (OR), 679 pregnancies and 528 babies born. Five hundred and fifty nine OR were reported for chromosomal abnormalities, 113 OR for sexing for X-linked diseases, 520 OR for monogenic diseases, 2087 OR for PGS, and 79 OR for social sexing. Data VII is compared with the cumulative data for data collections I-VI.

Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.

We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.

Testing genomic imprinting in Wilm's tumor.

Data from 511 cases of Wilms' tumor in France (including 12 familial cases) and 8 pedigrees from the literature were analyzed to test three modifications of Knudson's classical bimutational theory, based on genomic imprinting in Wilms' tumor carcinogenesis. Analysis of data of age at diagnosis and segregation analysis were performed to determine the number of independent events for Wilms' tumor development and to search for a differential role of paternal and maternal alleles. Unexpectedly, we show that only one rare event is required for tumor development in isolated unilateral cases which are considered to be mainly nonhereditary. In familial cases, we observe no effect of the sex of the transmitting parent on either hge at diagnosis or segregation ratio. We show that this could be explained by models of genomic imprinting which assume two nonindependent events, or only one rare genetic event. In bilateral cases we show a bimodality for age at diagnosis which could be due to a mixture of hereditary and nonhereditary cases. This result completely questions the classical assumption according to which all bilateral cases would be hereditary. These findings support the hypothesis that this childhood cancer arises from a variety of etiological pathways and might be useful to find strategies for further molecular investigations.

A clinical and genetic study of a manifesting heterozygote with X-linked myotubular myopathy.

X-linked myotubular myopathy (XLMTM) characteristically causes severe or fatal muscle weakness in male infants. Mutations in the gene MTM1, encoding the protein myotubularin, can be identified in most families. Prior to this report, XLMTM was thought not to cause symptomatic manifestations in female carriers. We describe an adult female from a large family with typical XLMTM. The patient had progressive disabling muscle weakness of later onset and lesser severity than that observed in affected males. The distribution of weakness resembled typical XLMTM with facial weakness, marked limb-girdle weakness, respiratory muscle involvement and dysphagia. Analysis of the MTM1 gene identified a heterozygous missense mutation (G378R) within the highly conserved tyrosine phosphatase site of myotubularin. We did not identify significantly skewed X-inactivation. We conclude that XLMTM is capable of causing significant disability in heterozygotes.

Cancers in relatives of children with non-Hodgkin's lymphoma.

We undertook a family study of children treated at the Institute Gustave-Roussy in France to investigate a familial aggregation of cancer in the families of children with non-Hodgkin's lymphoma (NHL). We obtained family dat for 284 children with NHL. Using the Standardized Incidence Ratio, we compared the observed and expected number of families with at least one proband relative affected by cancer at a young age (before 46 years). We found a small but non-significant excess of all tumors in first-degree relatives (SIR = 1.3, 95% CI = 0.7-2.3) explained by a small but non-significant excess of hematological malignancies (SIR = 1.5, 95% CI = 0.2-5.5), particularly Hodgkin's disease and leukemia, and of osteosarcoma (SIR = 7.5, 95% CI = 0.1-41.4). This is probably a lower bound of the SIR, because the expected number of families was estimated from cancer incidence in France between 1978 and 1982, whereas most cancers occurred before this period. Other tumors were not in excess in first-degree relatives.

[Preimplantation genetic diagnosis of monogenic diseases]. / Le diagnostic génétique préimplantatoire des maladies monogéniques.

Preimplantation genetic diagnosis (PGD) is an alternative to prenatal diagnosis allowing the detection of genetic diseases on IVF embryos before their transfer into the uterus and before the pregnancy. The aim of this procedure is to obtain unaffected or carrier embryos in order to avoid the burden of termination of pregnancy after prenatal diagnosis for couples at risk of transmitting particularly severe genetic disorders to their offspring. For monogenic diseases, PGD is most often based on single blastomere amplification by polymerase chain reaction (PCR). More than a decade after the first births, the possibilities of diagnosis for monogenic diseases have considerably increased. As for molecular biology and conventional diagnosis, the technologies and strategies for PGD are continually improved, with for instance introduction of fluorescent PCR or multiplex amplification. In this review, we describe several approaches for PGD of monogenic diseases, followed by an overview of the French practice, particularly in our lab.

[Twin birth after preimplantation diagnosis for cystic fibrosis]. / Naissance gémellaire après diagnostic préimplantatoire pour mucoviscidose.

OBJECTIVE: Cystic fibrosis is a common autosomal recessive disease most often caused by a deletion (delta F508) in the CFTR gene. It is the most common indication for preimplantaion genetic diagnosis which allows genetic analysis of embryos obtained after in vitro fertilization and transfer of unaffected embryos into the patient's uterus. PATIENTS AND METHODS: We report the first preimplantation genetic diagnosis performed in Strasbourg for a couple at risk of having a child affected by severe cystic fibrosis due to a homozygous delta F508 mutation. Three days after fertilisation, embryos obtained after intra-cytoplasmic testiculare sperm injection were biopsied and analysed. PCR amplification of the genomic fragment containing the delta F508 locus allowed detection of the delta F508 mutation and transfer only of the unaffected embryos. RESULTS: Three embryos were transferred after this preimplantation genetic diagnosis. A twin pregnancy was obtained and the babies born from this cycle are both exempt from the mutation. CONCLUSIONS: Preimplantation genetic diagnosis for the cystic fibrosis delta F508 mutation is now available in our centre. In this report, we could resolve both the problem of infertility and the risk of transmission of a severe form of cystic fibrosis. Preimplantation genetic diagnosis is also available for other mutations involved in cystic fibrosis and also for other genetic diseases.

[Fragile X syndrome is still unrecognized: efficacy of molecular diagnosis in mentally retarded probands]. / Le syndrome X fragile est encore méconnu: efficacité du diagnostic moléculaire chez les proposants avec retard mental.

BACKGROUND: The fragile X mental retardation syndrome is the most common cause of inherited mental retardation. Identification of the unstable mutation responsible for the disease has allowed the design of a fully reliable molecular test for the diagnosis of the disease and for genetic counselling (identification of clinically normal carriers and prenatal diagnosis). We started in July 1991 to search for the mutation in mentally retarded probands, with no known cause for their phenotype. We present the results of a 42-month experience. POPULATION AND METHODS: One thousand and one hundred fourty-nine probands were analysed. In case of a positive diagnosis, an extension of the molecular study to relatives was proposed. DNA samples were studied by Southern blot following EcoRI or EcoRI + EagI digestion. Clinical data were collected from referring clinicians. RESULTS: Seventy-three carriers of a full mutation were identified, belonging to 52 families. The mean age of the fragile X probands was 16 +/- 14 years, which is very surprising for a disease that causes significant manifestations by the age of 2 to 3 years. This indicates an insufficient knowledge about this disease in France. Most of the demands for the test were from clinical geneticists. This diagnosis is of major importance for genetic counselling, as illustrated by the following study of 108 women at risk in these families. CONCLUSIONS: The importance of an early diagnosis followed by an extended family study, for carrier screening and prevention of this severe disease, justifies molecular testing on any child with mental retardation or significant language delay of unknown cause, in the absence of clinical signs formally excluding a fragile X diagnosis.