A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B.

Individuals affected by pseudohypoparathyroidism type 1A (PHP1A) display hyperphosphatemia and hypocalcemia despite elevated PTH levels, as well as features of Albright Hereditary Osteodystrophy (AHO). PHP1A is caused by variants involving the maternal GNAS exons 1-13 encoding the stimulatory G protein α-subunit (Gsα). MLPA and aCGH analysis led in a male PHP1A patient to identification of a de novo 1284-bp deletion involving GNAS exon 1. This novel variant overlaps with a previously identified 1438-bp deletion in another PHP1A patient (ref. Li et al. (2020) [13], patient 2) that extends from the exon 1 promoter into the up-stream intronic region. This latter deletion is associated with reduced methylation at GNAS exon A/B, i.e. the differentially methylated region (DMR) that is demethylated in most pseudohypoparathyroidism type 1B (PHP1B) patients. In contrast, genomic DNA from our patient revealed no evidence for an epigenetic GNAS defect as determined by MS-MLPA and pyrosequencing. These findings thus reduce the region, which, in addition to other nucleotide sequences telomeric of exon A/B, may undergo histone modifications or interacts with transcription factors and possibly as-yet unknown proteins that are required for establishing the maternal methylation imprints at this site. Taken together, nucleotide deletions or changes within an approximately 1300-bp region telomeric of exon A/B could be a cause of PHP1B variants with complete or incomplete loss-of-methylation at the exon A/B DMR. In addition, when investigating patients with suspected PHP1A, MLPA should be considered to search for structural abnormalities within this difficult to analyze genomic region comprising GNAS exon 1.

Prospective Assessment of Pain and Comfort in Chronic Pain Patients Undergoing Interventional Pain Management Procedures.

Objective: Interventional pain management procedures have an important role in the management of chronic pain. The present study seeks to identify the proportion of patients who experience severe pain during pain procedures either with or without sedation. There is then an attempt to identify any association of high pain levels with factors such as age, gender, ethnicity, preprocedure pain level, procedure type, tobacco use, and baseline pharmaceuticals taken for both pain and/or mood disorder management. Methods: This is a prospective survey study evaluating patients' discomfort during interventional pain procedures in an outpatient academic facility. Patient discomfort was assessed by the PROcedural Sedation Assessment Survey (PROSAS) and modified for nonsedation cases. Results: There were 155 patients in the survey, with 20 of these receiving nonspinal injections. Of the remaining 135 patients who underwent spinal injections, only 10 received conscious sedation. On average, 14.2% experienced severe pain during spinal injections, whereas 20% experienced severe pain with nonspinal injections. Though few patients received conscious sedation, most of these (60%) experienced high levels of pain. There was no correlation between level of procedural pain with age, gender, ethnicity, preprocedure pain level, procedure type, tobacco use, or medication type used. Conclusions: The majority of patients who undergo nonsedated interventional pain management procedures do not experience severe pain. There is a small but appreciable group of subjects who seem to experience severe pain that cannot be correlated to any particular clinical characteristic in a standard patient evaluation. Even with standard conscious sedation, there is no clear best method to ensure patient comfort for this high-pain level group.