Autosomal recessive bestrophinopathy: new observations on the retinal phenotype - clinical and molecular report of an Italian family.

PURPOSE: To describe the genotype and phenotype in a 9-year-old boy with bilateral retinopathy. METHODS: The patient, his healthy (by history) nonconsanguineous parents and his sister were examined by best-corrected visual acuity, matrix frequency doubling technology, monocular static field analysis, fundus autofluorescence imaging, optical coherence tomography, Ganzfeld electroretinography (ERG), pattern ERG, multifocal ERG, electro-oculography and genotyping of the BEST1 gene. RESULTS: The patient presented with an Arden ratio of 1.25, an unremarkable ERG and fluorescent yellow deposits distributed throughout the fundus suggestive of autosomal recessive bestrophinopathy (ARB). Genotyping revealed a homozygous nonsense mutation in BEST1 (p.R200X). The parents and the sister, who were heterozygous mutation carriers, presented with normal ophthalmological function. CONCLUSIONS: ARB is a rare retinal disorder. We contribute a novel patient report indicative of ARB, assessed by clinical examination and confirmed by genotyping of BEST1, to the short list of ARB cases in the literature.

The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles.

BACKGROUND: The new Italian law, passed in 2004, regulating assisted reproduction technology imposes that no more than three oocytes can be fertilized at one time and that all embryos obtained must be transferred simultaneously. Oocyte cryopreservation is allowed while embryo cryostorage is banned. The aim of this study was to evaluate the clinical impact of these limitations. METHODS: Seven Italian infertility centres were invited to collect data on IVF cycles performed over the first 4 months of application of the new legislation. As a control, all centres provided data on cycles performed in the same solar period, 1 year before. RESULTS: Data from 1861 cycles were obtained, 961 in the pre-law period and 900 in the post-law period. Pregnancy rate per oocyte retrieval and rate of multiple pregnancies in the pre- and post-law periods were 27.0 and 24.2% (P=0.18) and 25.8 and 20.9% (P=0.11) respectively. However, the prohibition to freeze embryos does appear to have markedly reduced the cumulative rate of success. CONCLUSIONS: The rate of success of IVF-ICSI cycles using fresh embryos is not significantly influenced by the new legislation while the prohibition to freeze embryos seems to result in a more relevant impact.

Tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy and minihysteroscopy) versus hysterosalpingography in an outpatient infertility investigation.

OBJECTIVE: To compare the acceptance and tolerability of the mini-pan-endoscopic approach (transvaginal hydrolaparoscopy [THL] combined with minihysteroscopy) versus hysterosalpingography (HSG) for evaluating tubal patency and the uterine cavity in an outpatient infertility investigation. DESIGN: Randomized controlled study. SETTING: University hospital. PATIENT(S): Twenty-three infertile patients without obvious pelvic pathology. INTERVENTION(S): Women were randomly divided into two groups. One group underwent minihysteroscopy and THL with tube chromoperturbation as first investigation and HSG within the following 7 days, while in the other group the investigation sequence was inverted. Women reported pain experienced before and at the end of procedures. MAIN OUTCOME MEASURE(S): Mean duration of procedures, level of pain experienced, diagnostic agreement about tubal patency and uterine cavity normality. RESULT(S): THL and minihysteroscopy took significantly more time but was significantly less painful than HSG. Regarding tubal patency, in 95.5% of cases THL agreed with HSG. In one case, HSG diagnosed a bilateral obstruction of tubes, whereas at THL a bilateral spreading of methylene blue was seen. Agreement on intrauterine pathologies between minihysteroscopy and HSG was poor (43%); the number of intrauterine abnormalities found at hysteroscopy was significantly greater than at HSG. CONCLUSION(S): THL in association with minihysteroscopy provided more information and was better tolerated than HSG in an outpatient infertility investigation.

Trisomy 6q syndrome: a case with a << de novo >> 6q23 tandem duplication.

In this study, we report the combined use of whole and partial chromosome 6 painting probe and YACS probes to define the unbalanced region of a de novo 6q+ marker chromosome. A male patient with peculiar features of << distal 6q trisomy syndrome >> showed a direct duplication of 6q23 region. Comparing the phenotype of this child with the phenotype of other << de novo >> partial 6q trisomy, we conclude that band 6q23 has an important role in defining 6q trisomy.

Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21.

Developmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.

Breakpoint of a Y chromosome pericentric inversion in the DAZ gene area. A case report.

BACKGROUND: The presence of a spermatogenesis locus (gene or gene complex) in the euchromatic region of the long arm of the Y chromosome (Yq11), defined as azoospermia factor on the basis of gross structural rearrangement, was detected. The gene family responsible for different spermatogenetic defects is "deleted in azoospermia" (DAZ). CASE: A 34-year-old man had oligozoospermia, and a cytogenetic analysis carried out on peripheral lymphocytes with G banding revealed a 46,X, inv(Y)(p11q11)karyotype. The relation between the chromosomal breakpoint and the DAZ gene was more precisely defined by a fluorescent in situ hybridization technique. We revealed two signals for the DAZ gene, weaker than normal, one on the short arm and the other on the long arm of the Y chromosome, indicating that the breakpoint was located at the DAZ gene level. CONCLUSION: This is the first report documenting a chromosomal pericentric inversion with disruption in the DAZ gene area. We hope to obtain information on whether the disruption affects a functional zone of the gene and correlates with oligospermia at the chromosomal level.

Ovarian stimulation in a woman with premature ovarian failure and X-autosome translocation. A case report.

BACKGROUND: There are only a few reports on ovulation induction in women with premature ovarian failure resulting from an X chromosome abnormality. Up to now, there have been no publications on ovulation stimulation in a patient with an X-autosome translocation. CASE: A healthy, 29-year-old woman had premature ovarian failure (POF) but no other discernible pathologic clinical features. Laboratory tests prior to initiating a stimulation cycle revealed a 46,XX t(X;16) karyotype. Genetic counseling was proposed, and the risk of X chromosome abnormality was discussed. The couple decided to undergo ovulation induction. For treatment of infertility, clomiphene citrate had been administered in the past. Because those treatments were not successful, GnRH-a and follicle stimulating hormone treatment was recommended. The first treatment cycle was successful in inducing ovulation, but on the 15th day after human chorionic gonadotropin administration, menstruation occurred. The couple refused a second stimulation, and menstruation occurred 32 days after the first. The patient then became amenorrheic again. CONCLUSION: At least some hope can be offered to infertile women with hypergonadotropinism and X-autosomal translocation, although it is impossible to determine whether ovulation induction will result in pregnancy. New treatments can be anticipated for women with POF and X chromosome aberrations who have similar hormonal environments.

Intracytoplasmic sperm injection in infertile patients with structural cytogenetic abnormalities.

OBJECTIVE: To investigate the incidence of chromosomal aberration in men and women in an intracytoplasmic sperm injection (ICSI) program for severe male infertility as well as in conceptuses resulting from these ICSI treatments. STUDY DESIGN: We evaluated chromosomal analysis, outcome of ICSI and the conceptuses resulting from treatment of 301 couples included in ICSI program. RESULTS: Cytogenetic evaluation demonstrated structural anomalies in 11 cases (3.6%), 9 men (2.9%) and 2 women (0.7%), all consisting of balanced chromosomal translocations. There were no significant differences in the rates of developed embryos (44.2% versus 40.1%) in couples with abnormal (n = 11) and normal (n = 290) chromosomal analysis. Embryo transfer led to a similar number of newborns (15.3% versus 12.4%) per transferred embryos, without any correlation with parents' chromosomes. In 63 fetuses conceived from couples without chromosomal abnormalities, we observed one fetus affected by Patau syndrome (47,XY, + 13). Two of four (50%) fetuses conceived by couples with male balanced chromosomal defects were carriers of the chromosomal translocation inherited from their fathers. The two fetuses resulted in the birth of two infants observed to be normal at the 12-month pediatric follow-up. CONCLUSION: The offer of this treatment to infertile couples with male factor infertility should be accompanied by proper information regarding the genetic risks of this treatment. ICSI remains a good therapeutic option for infertile patients, but prenatal diagnosis is mandatory because of the potential increased aneusomic risk for the offspring conceived.

X/Y translocation in a family with Leri-Weill dyschondrosteosis.

An X/Y translocation associated with Leri-Weill dyschondrosteosis (LWD) was detected in a boy and in his mother. FISH analysis with specific probes for SHOX and SRY displayed no signal on the der(X), while one signal for SHOX was detected on the normal X chromosome in the mother, and one signal each for SHOX and SRY was detected on the normal Y chromosome in the proband.

Pseudodiastrophic dysplasia type Burgio in a newborn.

Pseudodiastrophic dysplasia is a distinct disorder that differs from diastrophic dysplasia on the basis of elbow and proximal interphalangeal joint dislocations, platyspondyly, and scoliosis. We report on a new patient with this rare skeletal dysplasia and two previously undescribed major malformations: omphalocele and complex heart defect.

[Abdominal pregnancy. An ever present challenge]. / La gravidanza addominale. Una sfida sempre attuale.

A case of abdominal pregnancy resulting from the rupture of the atresic horn of a bicornuate uterus and asymptomatic till the 23rd week of amenorrhea is reported. The peculiarities of this case lie in the advanced gestational age and in the association between two pathologies undoubtedly unusual as cornual and abdominal pregnancy. Discussion is focused on the limits of classical obstetrical semeiology, the possibilities of the instrumental examinations, the criteria that should guide decision-making and on the correct surgical management of this uncommon even if potentially life-threatening clinical pathology.

Techniques of sperm selection and in vitro fertilization results.

This study was performed to evaluate the effectiveness of four techniques for sperm selection in vitro fertilization (IVF) programme. Swim Up, Percoll, Sedimentation and Mini-Percoll were evaluated in 440 IVF cycles. The various methods were performed according to the motility and the number of spermatozoa, and the degree of cellularity of the sample; Swim Up and Percoll were used when sperm count was superior 20 million/ml, Sedimentation and Mini-Percoll when the sperm count was less than 20 million/ml. There was no difference in fertilization rate and in the number of replaced embryos per transfer with Swim Up compared to Percoll procedure; the Sedimentation technique improved fertilization (p < 0.05) and embryos rate (p < 0.001) compared to Mini-Percoll sperm preparation. There was no difference in pregnancy rate with Swim Up compared to Percoll and Sedimentation compared to Mini-Percoll procedure. We conclude that with advanced reproductive procedures where serious sperm disorders exist, the choose of the tecnique of sperm selection, most appropriate, according with the motility and the number of spermatozoa, the debrits and nonspermatic cells of the semen, might produce a suspension of spermatozoa with high fertilization potential.

Incidence and outcome of multiple pregnancy after in vitro fertilization.

The aim of this study was to analyse the experience of IVF multiple pregnancies, in relation to the maternal morbidity and the neonatal morbidity and mortality. We considered 48 multiple pregnancies: 36 twins (group A), 8 triplets (group B), 2 quadruplets (group C), and 2 quintuplets (group D). The mean maternal age was 29.72 years and the mean gestational age was 36.83 weeks. Of the 36 patients with two babies, 20 (55.60%) had cesarean section, whereas 12 were delivered vaginally. All the triplets, quadruplets and quintuplets were delivered abdominally. Twenty-three cervical cerclage were placed. In group A 7 patients had premature rupture of the membranes (PROM), 2 had pregnancy-induced hypertension (PIH) and 14 had premature labour. In group B 4 patients had premature labour, 3 hadPROM and 2 had PIH. In group C one patient had premature labour. In group D 2 patients had premature labour and one also PIH. Multiple pregnancies lead to a high incidence of antenatal complications and extensive neonatal morbidity which translate into prolonged and expensive hospitalization for the neonates.