title: Lamellar ichthyosis with pseudoexon activation in the transglutaminase 1 gene.
abstract: We report a case of a 12-year-old boy who was born as a collodion baby after which thick scales developed on his entire body surface. His younger brother showed a similar skin condition. Arcuate-shaped, large, brownish scales covered his face with ectropion. His lower legs were also covered with larger thick, brownish, plate-like scales, but other areas were covered with smaller scales. Next-generation sequencing for exons and splice sites detected a stop-gain TGM1 mutation leading to p.R71* in transglutaminase 1 (TG1). Another mutation identified was a cryptic mutation in intron 3 that activated a pseudoexon, which was detected by RNA-based analysis of hair bulbs. The deep intronic mutation caused another truncation mutation, p.N171Tfs(*) 45, in TG1. An in situ TG1 assay demonstrated that TG1 activity was totally lost in this case. Thus, we conclude that the severe phenotype of the patient developed due to those novel compound heterozygous null truncation mutations in TGM1.
authors: Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan.
authors: Yasushi
authors: Y
authors: Suga
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Tatsuya
authors: T
authors: Tsuda
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Makoto
authors: M
authors: Nagai
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Yoshiko
authors: Y
authors: Sakaguchi
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Orie
authors: O
authors: Jitsukawa
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Masaaki
authors: M
authors: Yamamoto
authors: Department of Basic Medical Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan.
authors: Kiyotaka
authors: K
authors: Hitomi
authors: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
authors: Kiyofumi
authors: K
authors: Yamanishi
mesh_terms: D002648:Child; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D007438:Introns; D008297:Male; D009154:Mutation; D011503:Transglutaminases / Q000235:genetics*
chemical_list: D011503:Transglutaminases; C105804:transglutaminase 1
keywords: lamellar ichthyosis; mutation; next-generation sequencing; pseudoexon; transglutaminase 1