Phenazopyridine-Induced Methemoglobinemia: A Case Report.

Methemoglobinemia is a condition caused by increased methemoglobin, a reduced form of hemoglobin, in the blood. This causes the molecules to bind oxygen more tightly and decreases their ability to release that oxygen to tissue. Most cases of methemoglobinemia are acquired and occur either in pediatric populations or in individuals with predisposing conditions. This report illustrates a case of an otherwise healthy 31-year-old patient presenting to the emergency department with cyanosis of the hands and mouth and an O2 saturation of 78% after taking increased doses of the over-the-counter medication phenazopyridine. A "chocolate-brown" color of her arterial blood, and increased methemoglobin levels of 20.2%, confirmed the diagnosis of methemoglobinemia. She was treated with both methylene blue and ascorbic acid, and her oxygen saturation and serum chemistry returned to normal levels within a few hours. The case highlights the importance of discussing the dosage of all over-the-counter medications with patients and recognizing the signs and symptoms of methemoglobinemia.

CRISPR/Cas9 interrogation of the mouse Pcdhg gene cluster reveals a crucial isoform-specific role for Pcdhgc4.

The mammalian Pcdhg gene cluster encodes a family of 22 cell adhesion molecules, the gamma-Protocadherins (γ-Pcdhs), critical for neuronal survival and neural circuit formation. The extent to which isoform diversity-a γ-Pcdh hallmark-is required for their functions remains unclear. We used a CRISPR/Cas9 approach to reduce isoform diversity, targeting each Pcdhg variable exon with pooled sgRNAs to generate an allelic series of 26 mouse lines with 1 to 21 isoforms disrupted via discrete indels at guide sites and/or larger deletions/rearrangements. Analysis of 5 mutant lines indicates that postnatal viability and neuronal survival do not require isoform diversity. Surprisingly, given reports that it might not independently engage in trans-interactions, we find that γC4, encoded by Pcdhgc4, is the only critical isoform. Because the human orthologue is the only PCDHG gene constrained in humans, our results indicate a conserved γC4 function that likely involves distinct molecular mechanisms.