Loss-of-Function Variants in SERPINA12 Underlie Autosomal Recessive Palmoplantar Keratoderma

The Proteolytic Network in Palmoplantar Keratoderma: SERPINA12 Joins the Family

“…Indeed, SERPINA12 is expressed in interfollicular epidermis (Toulza et al, 2007). Peeling affecting the cheek occurred in one case reported by Mohamad et al (2020), and facial peeling has previously been described in keratolytic winter erythema. This result may be consistent with the reports that the process of desquamation and the level of protease activity in facial skin is different from the nonpalmoplantar body sites.…”

“…More specifically, treatments could target SERPINA12, KLK7, and KLK14 levels. The SERPINA12 mutations described by Mohamad et al (2020) resulted in premature stop codons. The natural suppression of premature terminations (readthrough) could be augmented using readthroughenhancing drugs such as gentamicin, which could increase the expression of SERPINA12.…”

“…These include abnormalities in keratins, intercellular adhesion structures, and a variety of regulatory proteins, including proteases. Mohamad et al (2020) add loss-of-function mutations in SER-PINA12 to the growing list of potential causes for diffuse, autosomal recessive palmoplantar keratoderma (PPK).…”

Loss-of-function variants in KLF4 underlie autosomal dominant palmoplantar keratoderma

“…10,11 Different pathomechanisms may underlie defective function of adhesion proteins in hereditary PPK, including abnormal expression, function, or processing. 6,12,13 In this article, we report a novel form of PPK resulting from lossof-function variants affecting the ability of a critical transcription factor to regulate DSG1 expression.…”

Improved noninvasive fetal variant calling using standardized benchmarking approaches

“…Standard variant calling pipelines have been available for about one decade, and they have undergone continuous improvement during this time. Such pipelines have enabled us and other teams to detect countless deleterious mutations [27] , [28] , [29] , [30] , [31] . A number of studies have compared pipelines according to sequencing technologies, alignment software, post-alignment processing, and variant calling software [32] , [33] , [34] .…”