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Biomedical subjects

S Romana

Publications and source records attributed to S Romana.

At least 19 recordsLinked to original sources
PubMed2006

[Preimplantation genetic diagnosis (PGD): results from a Parisian center].

OBJECTIVE: To report the results of preimplantation genetic diagnosis (PGD) cycles performed in our unit from 2000 to 2004. Materials and methods. One hundred and seventy-one couples were enrolled in the PGD program over this period. The collected oocytes were inseminated by intracytoplasmic sperm injection (ICSI). The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Embryo transfers were carried out on the fourth day. RESULTS: The 416 stimulation cycles started yielded 280 oocyte pick-ups, 3506 oocytes retrieved, of which 2966 were suitable for ICSI. Among the 1982 embryos obtained, 1337 embryos were biopsied and genetic diagnosis was performed for 1083 (81%) of them. 381 embryos were transferred during the course of 189 transfer procedures. There were 51 clinical and 46 ongoing (35 single, 11 twin) pregnancies. In addition, 25 frozen embryo replacement cycles were initiated, leading to 6 embryo transfers and 1 ongoing pregnancy. A total of 58 unaffected children were born. CONCLUSION: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease. It might be a realistic alternative to prenatal diagnosis for patients carrier of chromosomal rearrangements, single gene defects, X-linked disesases or mitochondrial DNA disorders.

Adult↗
PubMed2005

[The Paris experience in preimplantation genetic diagnosis: evaluation after the first births].

OBJECTIVE: To report the birth of the first thirteen infants conceived after preimplantation genetic diagnosis (PGD) within the medical assistance federation of Paris. PATIENTS AND METHODS: Fifty-nine couples were enrolled between January 2000 and July 2001. They had a total of 71 oocyte pick-up cycles. The collected oocytes were inseminated by intracytoplasmic sperm injection. The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Most of the embryo transfers were carried out on the fourth day. RESULTS: The 71 oocyte pick-up cycles yielded 872 oocytes of which 731 were suitable for intracytoplasmic sperm injection. 421 embryos were biopsied and genetic diagnosis was obtained from 312 (74%) of these. 127 embryos were transferred during the course of 58 transfer procedures. There were 18 biologic and 12 clinical (7 singles, 4 twins and 1 triple) pregnancies. Thirteen infants have been born and 4 are expected. CONCLUSIONS: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease.

Blastocyst↗
PubMed2004

Classical West "syndrome" phenotype with a subtelomeric 4p trisomy.

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.

Abnormalities, Multiple↗
PubMed2004

Prenatal diagnosis and characterization of an analphoid marker chromosome 16.

We report on a fetus with intrauterine growth retardation and multiple malformations diagnosed on ultrasound at 32 weeks. Examination of amniotic fluid cells in culture showed a 47,XY, i(16)(q10), +mar karyotype. Chromosome analysis of both parents was normal. Using spectral karyotyping, we identified the marker chromosome as a mitotically stable acentric marker chromosome derived from chromosome 16. Further studies using subtelomeric fluorescent probes confirmed the presence of an isochromosome for the long arm of chromosome 16 and showed that the acentric marker chromosome derived from the short arm of chromosome 16 leading to a trisomy for the long arm of chromosome 16. After genetic counseling, the parents decided to terminate the pregnancy. Fetal autopsy showed a male fetus with ambiguous external genitalia, cardiac malformation, megacystis and limbs anomalies as observed in other cases of trisomy for the long arm of chromosome 16. In addition, fetal brain examination showed vermian and olfactory bulb hypoplasia.

Abnormalities, Multiple↗
PubMed2003

LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.

We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Mild phenotype in a 15-year-old boy with Pallister-Killian syndrome.

Pallister-Killian syndrome is a rare disorder characterized by multiple congenital anomalies, coarse face, pigmentary skin changes, seizures, severe mental retardation, and the presence of an extra metacentric chromosome i(12p) confined to skin fibroblasts only. Here, we report on an unusual case of i(12p) in a 15-year-old boy presenting with mild mental retardation, minor facial features (long face, prognathism, short neck), normal weight, length, and OFC parameters as well as hyperpigmented streaks. The boy attended normal school until the age of 14 years. Because of hyperpigmented stripes, chromosome analysis was performed on skin fibroblasts. This study showed that 37% of the cells had an additional isochromosome for the short arm of chromosome 12. This observation illustrates the phenotypic variability of i(12p) and emphasizes the importance of skin fibroblasts chromosome analysis in patients with pigmentary skin changes.

Abnormalities, Multiple↗
PubMed2003

[First birth after preimplantation genetic diagnosis performed on thawed embryos].

OBJECTIVE: To report the birth of the first infant conceived after preimplantation genetic diagnosis (PGD) performed on frozen-thawed embryos in our PGD center. PATIENTS AND METHODS: Three couples (C1, C2 and C3) who had frozen embryos from a previous in vitro fertilization attempt were enrolled in our PGD program. Embryos were thawed one day before the biopsy procedure for the couples C1 and C3 and the day of the biopsy for the couple C2. The single cell genetic analysis was performed by a multiplex PCR for the couple C1 and by fluorescent in situ hybridization for the couples C2 and C3. The embryos transfers were carried out on the third or fourth day. RESULTS: Out of ten thawed embryos, eight were biopsied and five were transferred during three embryos transfers. Two biochemical and one ongoing pregnancy were obtained yielded one birth. CONCLUSIONS: PGD may be offered to couples at risk of transmission of a serious and incurable genetic disease and having frozen embryos.

Biopsy↗
PubMed2002

[What's new in fetal medicine?].

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.

Adult↗
PubMed2002

Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation.

Recent studies have shown that cryptic unbalanced subtelomeric rearrangements contribute to a significant proportion of idiopathic syndromic mental retardation cases. Using a fluorescent genotyping based strategy, we found a 10% rate of cryptic subtelomeric rearrangements in a large series of 150 probands with severe idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype. Fourteen children were found to carry deletions or duplications of one or more chromosome telomeres and two children had uniparental disomy. This study clearly shows that fluorescent genotyping is a sensitive and cost effective method that not only detects cryptic subtelomeric rearrangements but also provides a unique opportunity to detect uniparental disomies. We suggest giving consideration to systematic examination of subtelomeric regions in the diagnostic work up of patients with unexplained syndromic mental retardation.

Child↗
PubMed2002

Congenital contractures, short stature, abnormal face, microcephaly, scoliosis, hip dislocation, and severe psychomotor retardation in two unrelated girls. a new MCA/MR syndrome?

Severe mental retardation, congenital contractures, short stature, microcephaly, ptosis, myopia, beaked nose, abnormal teeth, hip dislocation, and severe scoliosis, are described in a 16-year-old and an unrelated 24-year-old females. Results of all laboratory investigations were normal. Review of the literature, of the London Dysmorphology Data Base and POSSUM did not yield to any diagnosis. Whether these patients present a new MCA/MR syndrome is discussed.

Abnormalities, Multiple↗
PubMed2002

[Preimplantation genetic diagnosis experience in Paris: evaluation of first births].

OBJECTIVE: To report the birth of the first fourteen infants conceived after preimplantation genetic diagnosis (PGD) in our unit. PATIENTS AND METHODS: Fifty-nine couples were enrolled between January 2000 and July 2001. They had a total of 71 oocyte pick-up cycles. The collected oocytes were inseminated by intracytoplasmic sperm injection. The resulting embryos were biopsied on the third day of development and the genetic analysis was performed on the same day. Most of the embryo transfers were carried out on the fourth day. RESULTS: The 71 oocyte pick-up cycles yielded 872 oocytes of which 731 were suitable for intacytoplasmic sperm injection. Among the 505 embryos obtained, 421 embryos were biopsied and genetic diagnosis was performed for 312 (74%) of these. 127 embryos were transferred during the course of 58 transfer procedures. There were 18 biochemical and 12 ongoing (7 singles, 4 twins and 1 triple) pregnancies. Fourteen infants have been born and 2 are expected. CONCLUSION: PGD has gained a place among the choices offered to couples at risk of transmission of a serious and incurable genetic disease.

Adult↗
PubMed2001

Comparative genomic hybridisation in mentally retarded patients with dysmorphic features and a normal karyotype.

Segmental aneusomy for small chromosomal regions has been shown to be a common cause of mental retardation and multiple congenital anomalies. A screening method for such chromosome aberrations that are not detected using standard cytogenetic techniques is needed. Recent studies have focused on detection of subtle terminal chromosome aberrations using subtelomeric probes. This approach however excludes significant regions of the genome where submicroscopic rearrangements are also liable to occur. The aim of the present study was to evaluate the efficiency of comparative genomic hybridisation (CGH) for screening of submicroscopic chromosomal rearrangements. CGH was performed in a cohort of 17 patients (14 families) with mental retardation, dysmorphic features and a normal karyotype. Five subtle unbalanced rearrangements were identified in 7 patients. Subsequent FISH studies confirmed these results. Although no interstitial submicroscopic rearrangement was detected in this small series, the study emphasises the value of CGH as a screening approach to detect subtle chromosome rearrangements in mentally retarded patients with dysmorphic features and a normal karyotype.

Cytogenetic Analysis↗
PubMed2001

A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation.

Cryptic unbalanced subtelomeric rearrangements are known to cause a significant proportion of idiopathic mental retardation in childhood. Because of the limited sensitivity of routine analyses, the cytogenetic detection of such rearrangements requires molecular techniques, namely FISH and comparative genomic hybridisation (CGH). An alternative approach consists in using genetic markers to detect segmental aneusomy. Here, we describe a new strategy based upon automated fluorescent genotyping to search for non mendelian segregation of telomeric microsatellites. A total of 29 individuals belonging to 24 unrelated families were screened and three abnormal patterns of segregation were detected (two rearrangements and one parental disomy). This study gives strong support to the view that cryptic telomeric rearrangements significantly contribute to idiopathic mental retardation and demonstrates that fluorescent genotyping is a very sensitive and cost-effective method to detect deletions, duplications and uniparental disomies.

Child↗
PubMed2001

Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome.

OBJECTIVE: The objective was to determine the circadian rhythm of melatonin in the Smith-Magenis syndrome (SMS), which causes behavioral problems and sleep disturbance. STUDY DESIGN: Questionnaires, sleep consultations, and sleep diaries were obtained in 20 children with SMS (9 girls, 11 boys aged 4 to 17 years). Actigraphy, electroencephalography, and the circadian variations of plasma melatonin, cortisol, and growth hormone were recorded in 8 patients. Early sleep onset, early sleep offset, and sleep attack indicated sleep disturbance. RESULTS: All children with SMS had a phase shift of their circadian rhythm of melatonin. Time at onset of melatonin secretion was 6 AM +/- 2 (control group: 9 P.M. +/- 2). Peak time was 12 PM +/- 1 (control group: 3:30 AM +/- 1:30), and melatonin offset was at 8 PM +/- 1 (control group: 6 AM +/- 1). Behavioral problems correlated with the inverted circadian rhythm of melatonin. CONCLUSION: Considering that clock genes mediate the generation of circadian rhythms, we suggest that haploinsufficiency for a circadian system gene mapping to chromosome 17p11.2 may cause the inversion of the circadian rhythm of melatonin in SMS.

Abnormalities, Multiple↗
PubMed2001

Assisting reproduction of infertile men carrying a Robertsonian translocation.

BACKGROUND: In order to provide better genetic counselling for Robertsonian translocation carriers, the meiotic segregation of chromosomes 13, 14 and 21 from six infertile (13;14) and (14;21) Robertsonian translocation carriers was examined. METHODS: Dual-colour fluorescence in-situ hybridization analysis using locus-specific probes was carried out on spermatozoa of translocation carriers. Spermatozoa from six proven fertile subjects were analysed using the same probes as controls. RESULTS: We observed that the frequencies of unbalanced spermatozoa were similar in the (13;14) translocation carriers (9.0, 10.0 and 12.9%) and in the (14;21) translocation carriers (8.7, 7.2 and 7.0%). These frequencies were significantly increased compared with the control population (P < 0.05). CONCLUSIONS: This high frequency might justify the use of preimplantation genetic diagnosis in these patients where the translocation is usually associated with infertility, requiring intracytoplasmic sperm injection, as it might improve the outcome of the assisted reproduction technique.

Adult↗
PubMed2001

Absent lacrimal ducts, distichiasis, dysmorphic features, and brachydactyly: a case report.

We report a male patient presenting with the association of absent lacrimal ducts, distichiasis, dysmorphic facial features and limb abnormalities. Extensive chromosomal studies showed normal chromosomes. We discuss differential diagnoses such as Setleis, Char and Lacrimo-Auriculo-Dento-Digital (LADD) syndromes. This may represent a novel entity for which parental consanguinity would support an autosomal recessive mode of inheritance.

Abnormalities, Multiple↗