Case report: birth after preimplantation genetic diagnosis of a subtle mutation in SMN1 gene

Spinal muscular atrophy (SMA) preimplantation genetic diagnosis (PGD) has been available since 1998. Protocols are based on the detection of the homozygous deletion of exon 7, which are present in 90–98% of SMA patients. A couple where the woman was a heterozygous carrier of the usual SMN1 Del7 mutation and the man was a heterozygous carrier of pMet263Arg substitution in exon 6 of SMN1 gene was referred for PGD. The usual PGD test being unsuitable for this couple, we developed a novel duplex polymerase chain reaction (PCR)-based PGD test for the detection of the mutation pMet263Arg by allele specific amplification, combined with the amplification of D5S641 extragenic polymorphic marker. PCR conditions were established using single control lymphoblasts and lymphocytes from the pMet263Arg substitution carrier. Amplification was obtained in 100% of the 86 single cells tested, amplification refractory mutation system (ARMS) PCR was specific in 100% of single cells tested and a complete genotype (mutation plus D5S641) was achieved in 88% of them. A PGD cycle was performed successfully and a pregnancy was obtained. An unaffected girl was born and postnatal diagnosis confirmed PGD results. This is the first PGD described for SMA because of another mutation than the major homozygous exon 7 deletion of SMN1. In the future, a similar strategy could be adopted for other subtle mutations of this gene. Copyright © 2006 John Wiley & Sons, Ltd.     

Allele-specific amplification for preimplantation genetic diagnosis (PGD) of spinal muscular atrophy

We have developed a new allele-specific amplification method for the preimplantation genetic diagnosis (PGD) of spinal muscular atrophy (SMA; Werdnig-Hoffmann disease) from a single cell. This method is based on the detection of the deletion of exon 7 of the telomeric copy of the survival motor neurone (SMN^t) gene. An oligonucleotide was designed to be specific to the SMN^t nucleotidic sequence with exonic mismatch G (for SMN^t)→A (for SMN^c) at its 3′ end. This test produces reliable PCR products in 95% of single lymphoblasts (85/88) tested as well as in 16/16 blastomeres from normal controls. Specificity analysis showed that we were able to detect homozygous deletion of the SMN^t gene in 99% of single lymphoblasts (103/104) from a SMA patient. No contamination was detected in 68 blanks tested. Multiple cell and DNA dilution analysis revealed that the test is accurate and specific up to 100 pg DNA and should thus also be suitable for PGD at the blastocyst stage. This rapid procedure requires a single round of fluorescent PCR and no restriction digestion, while previously described single cell methods include nested PCR followed by restriction enzyme digestion. Two PGD cycles for SMA using this procedure were performed in our centre. Copyright © 2001 John Wiley & Sons, Ltd.     

Refuge‐Effect Hypothesis and the Demise of the Dodo

The Dodo was last sighted on the inshore island of Ile d'Ambre in 1662, nearly 25 years after the previous sighting on the mainland of Mauritius. It has been suggested that its survival on the inshore island is representative of the refuge effect. Understanding what constitutes significant persistence is fundamental to conservation. I tested the refuge‐effect hypothesis for the persistence of the Dodo (Raphus cucullatus) on an inshore island beyond that of the mainland population. For a location to be considered a refuge, most current definitions suggest that both spatial and temporal isolation from the cause of disturbance are required. These results suggest the island was not a refuge for the Dodo because the sighting in 1662 was not temporally isolated from that of the mainland sightings. Furthermore, with only approximately 350 m separating Ile d'Ambre from the mainland of Mauritius, it is unlikely this population of Dodos was spatially isolated. Hipótesis del Efecto Refugio y la Desaparición del Dodo     

Ultrasound demonstration of masses in a 15 week fetus: Hydrops in a fetus with umbilical cord occlusion

A fetal abnormality detected at 15 weeks by ultrasound consisted of cystic appearing masses in the neck and back region. The differential diagnosis included gonadal dysgenesis (Turner's syndrome) with cystic hygroma, neural tube defect, e.g. encephalocele or meningomyelocele, and fetal hydrops. Intrauterine fetal demise occurred at 17 weeks. The fetus had marked edema possibly related to umbilical cord occlusion.     

Delayed neurotoxicity of cyanofenphos in chickens

Abstract

Delayed neurotoxic ataxia, similar to that caused by neurotoxic organophosphorous compounds, has been shown to occur in hens after oral administration of Cyanofenphos (O‐ethyl‐O‐Cyanophenyl phenyl phosphonothionate) following either single or repeated oral doses. Axonal and myelin degeneration affecting the long tracts in spinal cord, peripheral nerves and medulla was demonstrated. The distal fibers with large diameters were particularly affected. This finding is a new contribution which has not been previously recorded. It implies that a thorough study of the structure‐activity relationships of phosphonothionates regarding their delayed neurotoxic effect is warranted.     

A Whole Body Postural Loading Simulation and Assessment Model for Workplace Analysis and Design

Abstract

This study reports on the development and validation of a new computer model for simulating human postures at work, and assessing the reaction forces and bending moments in 43 human articulation joints. The proposed model estimates the intradiscal pressure in the vertebral column in response to external loading forces encountered during human interactions with work objects or processes. The model was implemented in a self-contained interactive software package. The simulation results compare favorably with the reported experimental data, and provide reasonable confidence in the quality of the model. Its characteristics and its applications in evaluating physical task performance are also discussed     

Work conditions in agriculture as risk factors of spinal pain in postmenopausal women

The aim of the study was to evaluate the risk factors for spinal pain in Polish postmenopausal women working in agriculture. The study included 1751 randomly selected postmenopausal women aged 45–65?years. The women were exposed to hazardous work conditions, in particular the use of force and heavy lifting, often more than 10?kg and with frequency of at least once a day. Two-thirds of them suffered from spinal pain, mostly in the lumbar spine and less frequently in the cervical and thoracic spine. The prevalence of spinal pain depended on exposure to health risks associated with overwork, early onset of menopause and increasing age. The prevalence of pain in the lumbar spine correlated positively with higher frequency of heavy lifting and using excessive force during agricultural work. The severity of spinal pain correlates positively with the age of pain onset and negatively with level of education.