Whole-exome sequencing for diagnosis of Peters-plus syndrome after prenatal diagnosis of recurrent low PAPP-A and multiple fetal anomalies in two consecutive pregnancies.

 We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings. The importance and complexity of providing patient education to enable informed consent for next generation sequencing technologies is discussed.

Whole-exome sequencing for diagnosis of Peters-plus syndrome after prenatal diagnosis of recurrent low PAPP-A and multiple fetal anomalies in two consecutive pregnancies.

 We report a case of two consecutive pregnancies in the same couple presenting with very low pregnancy-associated plasma protein A (PAPP-A), with both pregnancies affected by multiple anomalies of a similar phenotype identified during mid-trimester ultrasound, and eventual diagnosis of Peters-plus syndrome. This case is important in expanding the differential for very low PAPP-A. It also demonstrates the diagnostic value of whole-exome sequencing (WES) after prenatal diagnosis of recurrent fetal ultrasonographic findings. The importance and complexity of providing patient education to enable informed consent for next generation sequencing technologies is discussed.

Seasonal changes in pancreatic B-cell function in euthermic yellow-bellied marmots.

Fasting plasma insulin (PI) and glucose (PG) concentrations were measured throughout the body weight cycle of marmots. Animals gained weight during summer, and in late fall body weight peaked, after which they ceased feeding. Each month euthermic animals were injected intra-arterially with either dextrose (500 mg/kg) or porcine insulin (0.1 U/kg), and blood samples were collected over the subsequent 2 h. During weight gain fasting PI concentration and pancreatic B-cell response to injected dextrose increased markedly. Maximal insulin release to a dextrose challenge was measured during peak body weight or when body weight initially began to decline. The PG concentration after exogenous insulin administration was slight (less than 10%) in the fall but increased approximately 25% in the spring after marmots lost weight. Basal PG levels were not significantly different throughout the year. Basal fasting PI concentrations were significantly higher during the fall (P less than 0.01). It is suggested that in the fall, when marmots are obese, hyperinsulinemia and peripheral insulin resistance appear. Furthermore, in two animals with an increase in body weight of approximately 30% or less over the summer, peripheral resistance was demonstrable, albeit not as marked as in animals that appropriately doubled their body weights when given food ad libitum. Thus we hypothesize that factors other than adiposity, i.e., food intake, central nervous system input to the pancreatic B-cell, and/or changes in B-cell sensitivity to PG, may contribute to the observed peripheral insulin resistance and may be involved in body weight regulation.

Plasma melatonin concentrations in hibernating marmots: absence of a plasma melatonin rhythm.

Plasma melatonin concentrations were measured throughout bouts of hibernation in marmots maintained in a short photoperiod (light-dark 8:16) and ambient temperature of 5 or 15 degrees C. Melatonin concentration was also measured in two animals maintained in constant darkness. As an animal entered hibernation, plasma melatonin concentrations dropped to basal levels when body temperature reached 25 degrees C, and they remained low until arousal. During deep hibernation plasma melatonin values did not vary significantly (P greater than 0.05) with respect to time of day or different ambient temperatures. With nocturnal arousal plasma melatonin levels were similar to euthermic night values. Lack of a plasma melatonin rhythm during hibernation suggests that the pineal gland is not temperature compensated during hibernation, and due to the low tissue temperature of the pineal the circadian pacemaker driving melatonin secretion is incapable of stimulating a rhythm.