Genotyping with a 198 Mutation Arrayed Primer Extension Array for Hereditary Hearing Loss: Assessment of Its Diagnostic Value for Medical Practice

Molecular diagnostic testing of individuals with congenital sensorineural hearing loss typically begins with DNA sequencing of the GJB2 gene. If the cause of the hearing loss is not identified in GJB2, additional testing can be ordered. However, the step-wise analysis of several genes often results in a protracted diagnostic process. The more comprehensive Hereditary Hearing Loss Arrayed Primer Extension microarray enables analysis of 198 mutations across eight genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, MTRNR1 and MTTS1) in a single test. To evaluate the added diagnostic value of this microarray for our ethnically diverse patient population, we tested 144 individuals with congenital sensorineural hearing loss who were negative for biallelic GJB2 or GJB6 mutations. The array successfully detected all GJB2 changes previously identified in the study group, confirming excellent assay performance. Additional mutations were identified in the SLC26A4, SLC26A5 and MTRNR1 genes of 12/144 individuals (8.3%), four of whom (2.8%) had genotypes consistent with pathogenicity. These results suggest that the current format of this microarray falls short of adding diagnostic value beyond the customary testing of GJB2, perhaps reflecting the array's limitations on the number of mutations included for each gene, but more likely resulting from unknown genetic contributors to this phenotype. We conclude that mutations in other hearing loss associated genes should be incorporated in the array as knowledge of the etiology of hearing loss evolves. Such future modification of the flexible configuration of the Hereditary Hearing Loss Arrayed Primer Extension microarray would improve its impact as a diagnostic tool

Catecholamine-Secreting Paragangliomas: Recent Progress in Diagnosis and Perioperative Management

Catecholamine-secreting paragangliomas (CSPs) present challenges for the managing team of surgeons and anesthesiologists. Without proper preoperative management and planning, the patient is at high risk for complications and significant morbidity. A review of the literature looking at all aspects of the care of patients with CSP was performed to provide a consensus on the comprehensive care of these difficult patients. A case study is also provided to illustrate the management algorithm. Specific recommendations are made with regards to preoperative workup, including serum and urine testing, tumor localization, angiography, and embolization. Preoperative and intraoperative management techniques by the surgical and anesthesiology teams are discussed, including pharmaceutical interventions and fluid management. Aspects of postoperative care are also discussed. Management of patients with CSP requires significant attention to detail by a multidisciplinary team of surgeons and anesthesiologists. By following the recommendations included within this article, the morbidity associated with removal of these tumors can be significantly reduced or eliminated