A single hole spin with enhanced coherence in natural silicon.

Semiconductor spin qubits based on spin-orbit states are responsive to electric field excitations, allowing for practical, fast and potentially scalable qubit control. Spin electric susceptibility, however, renders these qubits generally vulnerable to electrical noise, which limits their coherence time. Here we report on a spin-orbit qubit consisting of a single hole electrostatically confined in a natural silicon metal-oxide-semiconductor device. By varying the magnetic field orientation, we reveal the existence of operation sweet spots where the impact of charge noise is minimized while preserving an efficient electric-dipole spin control. We correspondingly observe an extension of the Hahn-echo coherence time up to 88 µs, exceeding by an order of magnitude existing values reported for hole spin qubits, and approaching the state-of-the-art for electron spin qubits with synthetic spin-orbit coupling in isotopically purified silicon. Our finding enhances the prospects of silicon-based hole spin qubits for scalable quantum information processing.

Fast Gate-Based Readout of Silicon Quantum Dots Using Josephson Parametric Amplification.

Spins in silicon quantum devices are promising candidates for large-scale quantum computing. Gate-based sensing of spin qubits offers a compact and scalable readout with high fidelity, however, further improvements in sensitivity are required to meet the fidelity thresholds and measurement timescales needed for the implementation of fast feedback in error correction protocols. Here, we combine radio-frequency gate-based sensing at 622 MHz with a Josephson parametric amplifier, that operates in the 500-800 MHz band, to reduce the integration time required to read the state of a silicon double quantum dot formed in a nanowire transistor. Based on our achieved signal-to-noise ratio, we estimate that singlet-triplet single-shot readout with an average fidelity of 99.7% could be performed in 1 µs, well below the requirements for fault-tolerant readout and 30 times faster than without the Josephson parametric amplifier. Additionally, the Josephson parametric amplifier allows operation at a lower radio-frequency power while maintaining identical signal-to-noise ratio. We determine a noise temperature of 200 mK with a contribution from the Josephson parametric amplifier (25%), cryogenic amplifier (25%) and the resonator (50%), showing routes to further increase the readout speed.

Gate-reflectometry dispersive readout and coherent control of a spin qubit in silicon.

Silicon spin qubits have emerged as a promising path to large-scale quantum processors. In this prospect, the development of scalable qubit readout schemes involving a minimal device overhead is a compelling step. Here we report the implementation of gate-coupled rf reflectometry for the dispersive readout of a fully functional spin qubit device. We use a p-type double-gate transistor made using industry-standard silicon technology. The first gate confines a hole quantum dot encoding the spin qubit, the second one a helper dot enabling readout. The qubit state is measured through the phase response of a lumped-element resonator to spin-selective interdot tunneling. The demonstrated qubit readout scheme requires no coupling to a Fermi reservoir, thereby offering a compact and potentially scalable solution whose operation may be extended above 1 K.

A CMOS silicon spin qubit.

Silicon, the main constituent of microprocessor chips, is emerging as a promising material for the realization of future quantum processors. Leveraging its well-established complementary metal-oxide-semiconductor (CMOS) technology would be a clear asset to the development of scalable quantum computing architectures and to their co-integration with classical control hardware. Here we report a silicon quantum bit (qubit) device made with an industry-standard fabrication process. The device consists of a two-gate, p-type transistor with an undoped channel. At low temperature, the first gate defines a quantum dot encoding a hole spin qubit, the second one a quantum dot used for the qubit read-out. All electrical, two-axis control of the spin qubit is achieved by applying a phase-tunable microwave modulation to the first gate. The demonstrated qubit functionality in a basic transistor-like device constitutes a promising step towards the elaboration of scalable spin qubit geometries in a readily exploitable CMOS platform.

Electrical Control of g-Factor in a Few-Hole Silicon Nanowire MOSFET.

Hole spins in silicon represent a promising yet barely explored direction for solid-state quantum computation, possibly combining long spin coherence, resulting from a reduced hyperfine interaction, and fast electrically driven qubit manipulation. Here we show that a silicon-nanowire field-effect transistor based on state-of-the-art silicon-on-insulator technology can be operated as a few-hole quantum dot. A detailed magnetotransport study of the first accessible hole reveals a g-factor with unexpectedly strong anisotropy and gate dependence. We infer that these two characteristics could enable an electrically driven g-tensor-modulation spin resonance with Rabi frequencies exceeding several hundred mega-Hertz.

Dispersively Detected Pauli Spin-Blockade in a Silicon Nanowire Field-Effect Transistor.

We report the dispersive readout of the spin state of a double quantum dot formed at the corner states of a silicon nanowire field-effect transistor. Two face-to-face top-gate electrodes allow us to independently tune the charge occupation of the quantum dot system down to the few-electron limit. We measure the charge stability of the double quantum dot in DC transport as well as dispersively via in situ gate-based radio frequency reflectometry, where one top-gate electrode is connected to a resonator. The latter removes the need for external charge sensors in quantum computing architectures and provides a compact way to readout the dispersive shift caused by changes in the quantum capacitance during inter-dot charge transitions. Here, we observe Pauli spin-blockade in the high-frequency response of the circuit at finite magnetic fields between singlet and triplet states. The blockade is lifted at higher magnetic fields when intra-dot triplet states become the ground state configuration. A line shape analysis of the dispersive phase shift reveals furthermore an intra-dot valley-orbit splitting Δvo of 145 µeV. Our results open up the possibility to operate compact complementary metal-oxide semiconductor (CMOS) technology as a singlet-triplet qubit and make split-gate silicon nanowire architectures an ideal candidate for the study of spin dynamics.

The coupled atom transistor.

We describe the first implementation of a coupled atom transistor where two shallow donors (P or As) are implanted in a nanoscale silicon nanowire and their electronic levels are controlled with three gate voltages. Transport spectroscopy through these donors placed in series is performed both at zero and microwave frequencies. The coherence of the charge transfer between the two donors is probed by Landau-Zener-Stückelberg interferometry. Single-charge transfer at zero bias (electron pumping) has been performed and the crossover between the adiabatic and non-adiabatic regimes is studied.

Embarazadas con lupus eritematoso sistémico en el hospital Clínico Regional de Concepción, Chile / Pregnant women with systemic lupus erythematosus in the Regional Clinical Hospital of Concepcion, Chile

Antecedentes: El lupus eritematoso sistémico (LES) afecta principalmente a mujeres en edad fértil. El embarazo en estas pacientes puede asociarse con múltiples complicaciones. Objetivo: Caracterizar a las embarazadas con LES durante 10 años en el Hospital Clínico Regional de Concepción. Métodos: Se realizó un estudio descriptivo retrospectivo que consistió en la revisión de fichas clínicas. Se analizaron las variables: edad, años de enfermedad desde el diagnóstico, historia obstétrica, presencia de reactivaciones, anticuerpos maternos y complicaciones materno-fetales. Resultados: Durante el periodo de estudio hubo 49 embarazos en 21 pacientes con LES. El 12,2 por ciento terminó en aborto, un 2 por ciento en óbitos, y un total de 43 nacidos vivos. La edad promedio de las pacientes al momento del diagnóstico de LES fue 24,5 años. El 67 por ciento fueron diagnosticadas antes de su primer embarazo. En el total de pacientes el 85,7 por ciento presentaron ANA positivo, 57,1 por ciento antiDNA positivo, 52,4 por ciento aRo positivo y 33,3 por ciento aLa positivo. En los caso de abortos, aRo y aLa se encontraban positivos en 66,7 por ciento. Las anticardiolipinas se encontraban alteradas en 33,3 por ciento de los abortos. Durante el embarazo el 32,6 por ciento tenía LES activo y 34,7 por ciento en el postparto. El 53,5 por ciento de los recién nacidos no tuvieron complicaciones. La complicación más frecuente fue la prematuridad con 55 por ciento. La mortalidad perinatal de la serie fue de 46,5/1000 nacidos vivos (2/43). No hubo muertes maternas. Conclusión: Es importante la educación respecto al embarazo en pacientes con LES. Debemos resaltar en promover que estas pacientes planifiquen el embarazo en periodo de inactividad, y con controles frecuentes para pesquisar precozmente cualquier complicación.

Background: The systemic lupus erythematosus (SLE) affects mainly fertile age women. Pregnancy in these patients can associate with multiple complications. Aims: To characterize the pregnant women with SLE during 10 years in the Hospital Clínico Regional de Concepción, Chile. Methods: We made a retrospective descriptive study which consisted in clinical files revision. The following variables were analyzed: age, years with disease since diagnose, obstetric history, history of reactivation, maternal antibodies and mother-fetus complications. Results: During the time of study there were 49 pregnancies on 21 patients with SLE; 12.2 percent ended in abortion, 2 percent in late fetal death giving a total of 43 living newborn. The average age of these patients at the moment of diagnose of LES was 24.5 years old; 67 percent were diagnosed before their first pregnancy. From the total of patients, 85.7 percent presented positive ANA, 57.1 percent positive antiDNA, positive aRo in 52.4 percent and positive aLa in 33.3 percent. In case of abortions, aRo and aLa were positive in 66.7 percent. Anticardiolipins were altered in 33.3 percent of abortions. During pregnancy 32.6 percent had active SLE, and 34.7 percent post-partum. Among the newborn, 53.5 percent did not have any complications. The most frequent complication was prematurity with a 55 percent. The perinatal mortality was 46.5/1000 lives births (2/43). There were no maternal deaths. Conclusion: It is important to educate about pregnancy in SLE patients. We must emphasize to promote in those patients a planned pregnancy in inactive period and with frequent controls for early diagnose of any complication.

Caracterización de recién nacidos reanimados durante el año 2011 en el Hospital Clínico Regional de Concepción / Characterization of neonatal resuscitation during 2011 at Regional Clinical Hospital of Concepcion

INTRODUCCIÓN: La asfixia es responsable del 19 por ciento de las muertes neonatales que ocurren en el mundo. La reanimación neonatal disminuye la mortalidad en estos Recién Nacidos (RN). 10 por ciento de los RN requieren maniobras de reanimación, de éstos, 1 por ciento requiere reanimación avanzada. OBJETIVOS: Caracterizar los RN reanimados durante el año 2011 en un hospital público. Materiales y métodos: Estudio descriptivo retrospectivo, con historias clínicas correspondientes a la totalidad de RN durante el 2011 en el Hospital Clínico Regional de Concepción. Se seleccionaron RN que requirieron maniobras de reanimación desde ventilación a presión positiva. Se analizaron datos demográficos, Apgar, maniobras realizadas y antecedentes maternos. RESULTADOS: Del total de RN vivos (4095) fueron reanimados 130 (3,17 por ciento), de estos últimos un 57,69 por ciento de término. El 11,5 por ciento fue de muy bajo peso y el 11,5 por ciento de extremo bajo peso al nacer. Hubo parto vaginal en 49,6 por ciento y cesárea urgencia 40,8 por ciento. En relación al Apgar al (1’) resultó <7 en 93,18 por ciento de los RN. Se utilizó Ventilación a Presión Positiva (VPP) en 66,15 por ciento; reanimándose sólo con aire un 12,9 por ciento de RN de término y todos los RN Pretérmino fueron reanimados con oxígeno, regulado por oximetría de pulso. Se realizó intubación endotraqueal en 26,92 por ciento; 6,92 por ciento requirió masaje cardiaco y medicamentos. El 96,15 por ciento sobrevivió y 48,15 por ciento fueron hospitalizados en UCI. DISCUSIÓN: El porcentaje de RN reanimados fue bajo en comparación a lo señalado en la literatura, pese a ser un centro de referencia. La mayoría de los reanimados fue de término. La maniobra más utilizada fue la VPP.

INTRODUCTION: Asphyxia is responsible for 19 percent of neonatal deaths that occur worldwide. Neonatal resuscitation contributes to lower morbidity and mortality in newborns. 10 percent of newborns require some assistance to begin breathing at birth; of this group less than 1 percent require extensive resuscitative measures. OBJECTIVE: To characterize newborns resuscitated during2011 in a public hospital. Material and method: Descriptive retrospective study, including all infants born during 2011 in Regional Clinical Hospital of Concepción. Neonates that required resuscitation measures were selected from positive ventilation pressure. Demographic data, Apgar score, resuscitation measures and maternal history were analyzed. RESULTS: Out of the 4095 living newborns, 130 of them (3.17 percent) were resuscitated. Of this group, 57.69 percent were of term gestation, 11.5 percent of them were very low weight and 11.5 percent extremely low weight. Vaginal delivery ocurred in 49.6 percent and urgency cesarean section in 40.8 percent. Apgar score at (1’) resulted <7 in 93.18 percent of neonates. Positive-pressure ventilation was used in 66.15 percent; using air in 12.9 percent of term infants. All preterm infants were resuscitated with oxygen, regulated by pulse oximetry. Endotracheal intubation was used in 6.92 percent; whereas 6.92 percent required cardiac massage and drugs. 96.15 percent survived and 48.15 percent were admitted to ICU. DISCUSSION: The percentage of resuscitated neonates was low in comparison to the pointed out in literature, despite being a reference center. The majority of resuscitated infants had term gestation. The most used resuscitation measure was positive pressure ventilation.

Coherent coupling of two dopants in a silicon nanowire probed by Landau-Zener-Stückelberg interferometry.

We report on microwave-driven coherent electron transfer between two coupled donors embedded in a silicon nanowire. By increasing the microwave frequency we observe a transition from incoherent to coherent driving revealed by the emergence of a Landau-Zener-Stückelberg quantum interference pattern of the measured current through the donors. This interference pattern is fitted to extract characteristic parameters of the double-donor system. In particular we estimate a charge dephasing time of 0.3±0.1 ns, comparable to other types of charge-based two-level systems. The demonstrated coherent coupling between two dopants is an important step towards donor-based quantum computing devices in silicon.

[Economic and organizational impact of the use of a disposable sheath with a flexible cystoscope]. / Cystoscope flexible à gaine stérile à usage unique: impact organisationnel et économique et sécurité bactériologique.

PURPOSE: To assess both economical and organizational impact as well as bacteriologic safety of a flexible cystoscope with sterile disposable sheath (FCSDS) compared to standard flexible cystoscopy (SFC) in two French urologic academic units. PATIENTS: Two-center prospective study, comparing the use of the FCSDS to the SFC on two consecutive periods of time. Two hundred and five patients were included and divided into each group. Duration procedures and costs were analysed in the two techniques. The urinary tract infection rate was also described. A dedicated sheaths leaks test after use was performed systematically. RESULTS: The preparation time of the fibroscope was longer for the sheathed cystoscopy group: 16.2 minutes versus 10.9 minutes for the standard group. The mean duration of disinfection was significantly shorter for the sheathed cystoscopy group: 53.8 minutes saved compared to the standard group; 99.01% of the tested sheaths, after their use, had no breaches. Urinary tract infections rate were similar in the two groups. The average cost of a sheathed cystoscopy compared to the standard was significantly cheaper in Lyon and almost equivalent in Marseille. CONCLUSION: The FCSDS allows significant saving over the disinfection duration, consumable costs and staff costs, while ensuring patient bacteriologic safety similar to SFC.

A two-atom electron pump.

With the development of single-atom transistors, consisting of single dopants, nanofabrication has reached an extreme level of miniaturization. Promising functionalities for future nanoelectronic devices are based on the possibility of coupling several of these dopants to each other. This already allowed to perform spectroscopy of the donor state by d.c. electrical transport. The next step, namely manipulating a single electron over two dopants, remains a challenge. Here we demonstrate electron pumping through two phosphorus donors in series implanted in a silicon nanowire. While quantized pumping is achieved in the low-frequency adiabatic regime, we observe remarkable features at higher frequency when the charge transfer is limited either by the tunnelling rates to the electrodes or between the two donors. The transitions between quantum states are modelled involving a Landau-Zener transition, allowing to reproduce in detail the characteristic signatures observed in the non-adiabatic regime.

[Does PCA3 score and prostatic MRI help selection of patients scheduled for initial prostatic biopsy?]. / Le score PCA3 et l'IRM prostatique permettent-ils de sélectionner les patients candidats a une première série de biopsies prostatiques ?

INTRODUCTION: Determinate if the adjunction of PCA3 score and/or prostatic MRI can improve the selection of the patients who have an indication of first prostate biopsy. PATIENTS AND METHODS: Multiparametric prostatic MRI and PCA3 score were made before biopsy to men scheduled for initial prostate biopsy for abnormal digital rectal examination and/or PSA superior to 4 ng/mL. T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced imaging looked for suspect target classified on a scale of four. It was a prospective, single centre study. The diagnostic accuracy of PCA3 score and MRI was to evaluate in comparison with biopsy results. RESULTS: Sixty-eight patients were included, median PSA was 5.2 ng/mL (3.2-28). Negative predictive value (NPV) of MRI score 0, 1 and 2 were respectively 80%, 43% and 69%. Positive predictive value (PPV) of MRI score 3 and 4 were 50% and 81%. The PCA3 cutoff with best accuracy was 21 (Se: 0.91; Sp: 0.50). Only one patient with positive biopsy (0.5mm of Gleason score 3+3) had negative MRI and PCA3 inferior to 21. CONCLUSION: MRI and PCA3 score in association allowed, in this study, to consider reduction of unnecessary initial biopsy without ignoring potential aggressive tumor.

Detection of a large valley-orbit splitting in silicon with two-donor spectroscopy.

We measure a large valley-orbit splitting for shallow isolated phosphorus donors in a silicon gated nanowire. This splitting is close to the bulk value and well above previous reports in silicon nanostructures. It was determined using a double dopant transport spectroscopy which eliminates artifacts induced by the environment. Quantitative simulations taking into account the position of the donors with respect to the Si/SiO2 interface and electric field in the wire show that the values found are consistent with the device geometry.

Prevalencia de dislipidemias en los pacientes con lupus eritematoso sistémico en el Hospital Clínico Regional de Concepción / Prevalence of dyslipidemia in patients with systemic lupus erythematosus in Hospital Clínico Regional of Concepción

INTRODUCCIÓN: El lupus eritematoso sistémico es considerado un factor de riesgo cardiovascular. En estos pacientes es frecuente hallar dislipidemias. La terapia corticoesteroide favorece las alteraciones lipídicas. HIPÓTESIS: Los pacientes con lupus eritematoso sistémico presentan hipercolesterolemia, hipertrigliceridemia o ambos, en mayor proporción que la población general. OBJETIVO: Determinar la prevalencia de dislipidemias en los pacientes diagnosticados de lupus eritematoso sistémico y controlados en el policlínico de reumatología del Hospital Clínico Regional de Concepción. MATERIAL Y MÉTODO: Estudio descriptivo transversal en pacientes diagnosticados de lupus eritematoso sistémico, y que se han controlado durante el 2010 en el policlínico de reumatología. Las variables estudiadas fueron: sexo, edad, hipercolesterolemia, hipertrigliceridemia, dosis/ tiempo de uso de corticoides e hidroxicloroquina. RESULTADOS: Total de pacientes estudiados (n=154), 88,9 por ciento (n=137) mujeres, edad promedio45,6 + 5 años, 40,9 por ciento (n=43) presenta hipertrigliceridemia; 55,2 por ciento (n=58) presenta hipercolesterolemia y 65,9 por ciento (n=100) presenta ambas alteraciones. Pacientes con evolución menor de 10 años: 50 por ciento (n=29) presenta hipercolesterolemia, 34,5 por ciento (n=20) presentaba hipertrigliceridemia; con 11-20 años de evolución: 56,25 por ciento (n=18) presenta hipercolesterolemia.; 43,75 por ciento (n=14) presenta hipertrigliceridemia Con evolución mayor a 20 años: 73,3 por ciento (n=11) presenta hipercolesterolemia; 60 por ciento (n=9) presentaba hipertrigliceridemia Usuarios de corticoides 89 por ciento (n=138) y de hidroxicloroquina 92,4 por ciento (n=142). DISCUSIÓN: La principal alteración es hipercolesterolemia. Pacientes con más años de evolución presentan mayor número de dislipidemias. La mayoría son usuarios de corticoides. Concluimos que la prevalencia de...

INTRODUCTION: Systemic lupus erythematosus is considered a cardiovascular risk factor. Dyslipidemia is commonly found in these patients. Corticosteroid therapy promotes lipid abnormalities. HYPOTHESES: Systemic lupus erythematosus patients with hypercholesterolemia, hypertriglyceridemia, or both, in greater proportion than the general population. OBJECTIVE: To determine the prevalence of dyslipidemia in patients diagnosed with systemic lupus erythematosus and monitored at the clinic of rheumatology, Hospital Clínico Regional Concepción. MATERIAL AND METHOD: A retrospective cross sectional in patients diagnosed with systemic lupus erythematosus and have controlled the last year in the Hospital Clínico Regional Concepción. The variables studied were: sex, age, hypercholesterolemia, hypertriglyceridemia, dose/duration of use of corticosteroids and hydroxichloroquine. RESULTS: Of all patients studied (n=154), 88.9 percent (n=137) women, mean age 45.6 +/- 5 years, 40.9 percent (n=43) presents hypertriglyceridemia, 55.2 percent (n=58) presented hypercholesterolemia presented and 65.9 percent (n=100) presented both alterations. Patients with minor changes 10 years: 50 percent (n=29) presents hypercholesterolemia; 34.5 percent (n=20) had hypertriglyceridemia. With11-20 years of evolution: 56.25 percent (n=18) presents hypercholesterolemia;45.75 percent (n=14) has hypertriglyceridemia. With over 20years of evolution: 73.3 percent (n=11) has hypercholesterolemia; 60 percent(n=9) showed hypertriglyceridemia. Steroids users 89 percent (n=138)and 92.4 percent (n=142) using hixychloroquine. DISCUSSION: The main alteration is hypercholesterolemia. Patients with more years of evolution have a greater number of dyslipidemia than others patients. Most are steroid users. We conclude that the prevalence of dyslipidemia is more common in systemic lupus erythematosus patients than the general population...

Single-donor ionization energies in a nanoscale CMOS channel.

One consequence of the continued downward scaling of transistors is the reliance on only a few discrete atoms to dope the channel, and random fluctuations in the number of these dopants are already a major issue in the microelectronics industry. Although single dopant signatures have been observed at low temperatures, the impact on transistor performance of a single dopant atom at room temperature is not well understood. Here, we show that a single arsenic dopant atom dramatically affects the off-state room-temperature behaviour of a short-channel field-effect transistor fabricated with standard microelectronics processes. The ionization energy of the dopant is measured to be much larger than it is in bulk, due to its proximity to the buried oxide, and this explains the large current below threshold and large variability in ultra-scaled transistors. The results also suggest a path to incorporating quantum functionalities into silicon CMOS devices through manipulation of single donor orbitals.

Doublecortin interacts with mu subunits of clathrin adaptor complexes in the developing nervous system.

Doublecortin is a microtubule-associated protein required for normal corticogenesis in the developing brain. We carried out a yeast two-hybrid screen to identify interacting proteins. One of the isolated clones encodes the mu1 subunit of the adaptor complex AP-1 involved in clathrin-dependent protein sorting. We found that Doublecortin also interacts in yeast with mu2 from the AP-2 complex. Mutagenesis and pull-down experiments showed that these interactions were mediated through a tyrosine-based sorting signal (YLPL) in the C-terminal part of Doublecortin. The functional relevance of these interactions was suggested by the coimmunoprecipitation of Doublecortin with AP-1 and AP-2 from mouse brain extracts. This interaction was further supported by RNA in situ hybridization and immunofluorescence studies. Taken together these data indicate that a certain proportion of Doublecortin interacts with AP-1 and/or AP-2 in vivo and are consistent with a potential involvement of Doublecortin in protein sorting or vesicular trafficking.

Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation.

We have recently shown that mutations in oligophrenin-1 (OPHN1) are responsible for non-specific X-linked mental retardation (MRX). The structure of the gene encoding the OPHN1 protein was determined by isolation of genomic DNA clones from the human cosmid library. Genomic fragments containing exons were sequenced, and the sequences of the exons and flanking introns were defined. Knowledge of the genomic structure of the OPHN1 gene, which spans at least 500 kb and consists of 25 exons, will facilitate the search for additional mutations in OPHN1. OPHN1 was screened for mutations in 164 subjects with non-specific mental retardation. Three nucleotide substitutions were identified, one of which was a silent mutation in the codon threonine 301 at position 903 (G-->C). The other substitutions were located in exon 2, a G-->A substitution at position 133 (A45T), and in exon 10, a C-->T substitution at position 902 (T301M), but these are common polymorphisms rather than disease-causing mutations.

MECP2 mutations account for most cases of typical forms of Rett syndrome.

Rett syndrome (RTT) is a severe progressive neurological disorder that affects almost exclusively females, with an estimated prevalence of approximately one in 10 000-15 000 female births. Most cases are sporadic, but several reports about familial recurrence support X-linked dominant inheritance with male lethality. The gene responsible for this disorder, MECP2, was recently identified by candidate gene strategy. Mutations were detected in <25% of RTT cases in this first report. To characterize the spectrum of mutations in the MECP2 gene in RTT patients, we selected 46 typical RTT patients and performed mutation screening by denaturing gradient gel electrophoresis combined with direct sequencing. We identified 30 mutations, accounting for 65% of RTT patients. They include 12 novel mutations (11 located in exon 3 and one in exon 2). Mutations, such as R270X and frameshift deletions in a (CCACC) (n) rich region, have been found with multiple recurrences. Most of the mutations were de novo, except in one family where the non-affected transmitter mother exhibited a bias of X inactivation. Although this study showed that MECP2 mutations account for most cases of typical forms of RTT (65%) and mutations in non-coding regions cannot be excluded for the remaining cases, an alternative hypothesis that takes into account the homogeneous phenotype and exclusive involvement of females, could be the implication in RTT of a putative second X-linked gene.