PMC:4157147 / 2622-3861 JSONTXT

{"project":"2_test","denotations":[{"id":"25152456-12175488-2045829","span":{"begin":43,"end":45},"obj":"12175488"},{"id":"25152456-12393799-2045830","span":{"begin":163,"end":165},"obj":"12393799"},{"id":"25152456-23813623-2045830","span":{"begin":163,"end":165},"obj":"23813623"},{"id":"25152456-17921507-2045831","span":{"begin":304,"end":306},"obj":"17921507"},{"id":"25152456-21610158-2045831","span":{"begin":304,"end":306},"obj":"21610158"},{"id":"25152456-24131873-2045831","span":{"begin":304,"end":306},"obj":"24131873"},{"id":"25152456-17921507-2045832","span":{"begin":487,"end":489},"obj":"17921507"},{"id":"25152456-20654612-2045832","span":{"begin":487,"end":489},"obj":"20654612"},{"id":"25152456-21610158-2045833","span":{"begin":569,"end":571},"obj":"21610158"},{"id":"25152456-18288204-2045834","span":{"begin":748,"end":750},"obj":"18288204"},{"id":"25152456-15831758-2045835","span":{"begin":868,"end":870},"obj":"15831758"}],"text":"GRHL2 is also present in the cochlear duct,14 and mutations in human GRHL2 have been found in progressive autosomal-dominant hearing loss (DFNA28 [MIM 608641]),15,16 and other polymorphic sequence variants in GRHL2 have been implicated in age-related hearing impairment and noise-induced hearing loss.17–19 To date, however, the role of GRHL2 in skin biology has not been well established. Causing severe facial and neural-tube defects, Grhl2 knockout is embryonically lethal in mice,17,20 and mutant zebrafish display inner-ear defects and abnormal swimming positions.18 In contrast, Grhl1−/− mice show hair loss and palmoplantar keratoderma, as well as abnormal desmosome cell junctions and dysregulated terminal differentiation in keratinocytes.21 Moreover, Grhl3−/− embryos fail to establish a normal epidermal barrier and display defective embryonic wound repair.22 Thus, unlike for GRHL1 and GRHL3, there is currently a lack of data associating GRHL2 with skin pathology. In this report, however, we have identified two families in which affected subjects have developmental defects affecting skin, oral mucosa, and teeth (as well as hearing and lungs), thus implicating GRHL2 in an autosomal-recessive ectodermal dysplasia syndrome."}