LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in mice, Lmx1b has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of Lmx1b appears adequate for development, Lmx1b null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In Lmx1b functional knockouts (KOs), Lmx1b transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved Lmx1b-associated cis-regulatory modules (LARM1 and LARM2) that are bound by Lmx1b, amplify Lmx1b expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal LMX1B coding sequence, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis.

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The field of dermatology and syphilology has relied on diagnostic laboratory and pathology tools to aid in the clinician in care of the patient for the better part of two centuries. The purpose of the diagnostics in dermatology column is to highlight commonly encountered diagnostic tools in dermatology and review the indications for use and result interpretation. This article discusses the anal Pap smear, a useful and cost-effective tool to screen for anal intraepithelial neoplasia in at-risk groups.

A drug is defined in physiology as being a substance that exerts an effect on the body once it has been ingested or otherwise introduced. Drugs are administered in many forms, which include (but are not limited to) a variety of oral and topical preparations. The purpose of this column was to take a closer look at drugs that are used in the field of dermatology. More specifically, this column hopes to bring an understanding to the reader regarding mechanism of action, administration, dosage, adverse effects, contraindications, and viable alternatives to each particular drug being discussed. In this article, tranexamic acid and its use as a dermatologic treatment for melasma, as well as other treatment modalities, will be discussed.