Single-nucleotide polymorphism-based chromosomal microarray analysis provides clues and insights into disease mechanisms.

OBJECTIVE: Chromosomal microarray analysis (CMA) is the modality of choice for prenatal diagnosis in pregnancy with fetal malformation, as it has a high diagnostic yield for microdeletion/duplication syndromes. The aim of this study was to demonstrate the additional utility of single-nucleotide polymorphism (SNP)-based CMA in diagnosing monogenic diseases, imprinting disorders and uniparental disomy (UPD). METHODS: CMA was performed using Affymetrix CytoScan array, for all indications in 6995 pregnancies, at a tertiary referral hospital from November 2013 to June 2018. We describe four cases that had a CMA result that provided a more comprehensive understanding of the complex genetic mechanisms underlying the clinical presentation. RESULTS: In the first fetus, CMA was performed due to intrauterine growth restriction and revealed a 75 kbp maternally inherited microdeletion encompassing the Bloom syndrome gene (BLM). A diagnosis of Bloom syndrome was made upon identifying a paternally inherited common Ashkenazi founder mutation. In the second case, CMA was performed due to severely abnormal maternal serum analytes and revealed a deletion in 14q32.2q32.31 on the maternally inherited copy, leading to a diagnosis of Kagami-Ogata syndrome, which is an imprinting disorder. In the third case, amniocentesis was performed because of late-onset fetal macrosomia and mild polyhydramnios. CMA detected a deletion encompassing the locus of Prader-Willi/Angelman syndrome. In the fourth case, amniocentesis was performed due to maternal cytomegalovirus seroconversion. Maternal UPD of the entire long arm of chromosome 11 was detected. CONCLUSION: Prenatal CMA, based on oligo and SNP platforms, increases the diagnostic yield and enables a wider spectrum of disorders to be detected through the identification of complex genetic etiologies beyond only copy number variants. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Preimplantation genetic diagnosis for BRCA1/2--a novel clinical experience.

OBJECTIVE: To describe our 2-year experience with preimplantation genetic diagnosis (PGD) for carriers of mutations in the genes BRCA1 and BRCA2, the dilemmas incurred and the lessons learned. METHODS: We collected data on those carriers of BRCA1/2 mutations who applied for PGD counseling and who decided to proceed. We describe the PGD procedures that were conducted and their outcome. RESULTS: Ten carriers of BRCA1/2 mutations applied for PGD counseling, seven were healthy, and three were BC survivors. Eight women needed in vitro fertilization (IVF) because of coexisting infertility. After counseling, six opted for the procedure and five of them underwent PGD for the BRCA mutation. In one of these PGD, fluorescence in situ hybridization (FISH) analysis for chromosomes 21, X and Y was also performed. Three women conceived, each in the first treatment attempt. One of them gave birth to twins, the second to a singleton and the third is currently pregnant. During the pregnancies, dilemmas concerning PGD confirmation were discussed. CONCLUSIONS: PGD is an acceptable reproductive option for BRCA mutation carriers, especially for those who require IVF due to fertility problems. Discussion of this option should be carried out with sensitivity, taking into account the age of the woman, her health, fertility status and emotional state. Confirmatory prenatal diagnosis may not always be encouraged.

Efficacy of pralidoxime iodide and obidoxime dichloride as antidotes in diazinon-poisoned goslings.

The antidotal efficacy of pralidoxime iodide and obidoxime dichloride was investigated in goslings poisoned by a supralethal dose of the organophosphorus insecticide diazinon. Various doses of both drugs were administered by intramuscular injection when the poisoned birds were unable to walk. Pralidoxime at 100 mg/kg brought about a complete and speedy clinical recovery. Fifty mg/kg induced recovery in 4 of 6 poisoned goslings, and 25 mg/kg successfully trated only 1 of 6 birds. Obidoxime at 25 mg/kg showed no therapeutic properties whereas 50 and 100 mg/kg delayed the death of some birds by several hours. At 100 mg/kg, all goslings had transient signs of intoxication, which precluded the use of this compound as an antidote at higher doses. The mode of action of these antidotes in diazinon-poisoned goslings is discussed.

Chronic lesions in geese photosensitized by Ammi majus.

Chronic lesions of the beak, footweb, and eye of geese photosensitized by the comsumption of Ammi majus (L.) are described, 7 weeks after the acute symptoms commenced. Sixty-four (48%) of the 133 birds in the flock showed various degrees of abnormality. All affected birds had stunting of the upper beak and cicatrization and thickening of the footweb. Eighty-nine percent of the affected birds showed ocular involvement, comprising chemosis, blepharoconjunctivitis, keratitis, symblepharon, ankyloblepharon, cicatricial ectropium, and mydriasis.

The susceptibility of young chickens, ducks, and turkeys to the photosensitizing effect of Ammi visnaga seeds.

Young chickens, ducks, and turkeys were exposed to sunlight and fed various amounts of Ammi visnaga seeds for 14 days in an attempt to induce photosensitization. In chickens, seeds at 1.25% in the diet had no effect whereas 3% induced mild signs of photosensitization within 6 to 8 days. No visible effects resulted in ducklings from 1.5, 3 and 6% in the diet, or in turkey poults from 3%. These differences appear to be due to differences between these avian species in the metabolism of the photodynamic agent.

Histology of the iris in geese and ducks photosensitized by ingestion of Ammi majus seeds.

Geese and ducks were photosensitized by the ingestion of Ammi majus seeds, and exposure to sunlight. Mydriasis was a characteristic clinical feature of this syndrome in both species. Histologically the iris of the affected birds showed vacuolisation and varying degrees of atrophy of the muscle of the sphincter pupillae. The effect of pilocarpine and physostigmine on the normal and mydriatic eyes was studied. The possible mode of action of photosensitization and the significance of these findings in the light of the use of psoralens in human medicine is discussed.

Acute and chronic manifestations of Ammi majus induced photosensitisation in ducks.

The acute and chronic symptoms seen in ducks following Ammi majus induced photosensitisation are described. The acute changes were inflammatory in nature whereas the chronic changes included severe deformities of the beak and footwebs, mydriasis and eccentric location of the pupil.