PMID- 29689068
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20210109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 4
DP  - 2018
TI  - Role of the keratin 1 and keratin 10 tails in the pathogenesis of ichthyosis 
      hystrix of Curth Macklin.
PG  - e0195792
LID - 10.1371/journal.pone.0195792 [doi]
LID - e0195792
AB  - Ichthyosis Hystrix of Curth-Macklin (IH-CM) is a rare manifestation of 
      epidermolytic ichthyosis (EI) that is characterised by generalised spiky or 
      verrucous hyperkeratosis. The disorder is further distinguished by the presence 
      of binucleated cells in the affected skin, whereas epidermolysis and clumping of 
      tonofilaments, as seen in EI, are absent. While IH-CM is associated with 
      mutations in the keratin 1 (KRT1) gene, reports to date have indicated that 
      mutations in the KRT1 gene result in an aberrant and truncated protein tail, 
      essentially affecting the function of the V2 domain. Here, we studied a female 
      sporadic patient who was born with diffused erythrodermic hyperkeratosis and who 
      presented at the age of 13 months with an intense and widespread hyperkeratosis 
      with a papillomatous appearance and typical palmoplantar keratoderma. Genetic 
      analysis demonstrated a "de novo" mutation in the keratin 10 gene (KRT10) 
      consisting of a three-base-pair deletion, resulting in the substitution of amino 
      acids p.Glu445 and p.Ile446 by Asp at the end of the 2B domain of the protein. We 
      performed structural and functional studies showing that this mutation modifies 
      the structure of the paired 2B and V2 K1/10 domains, leading to the disease 
      phenotype. Our results highlight the importance and complexity of the KRT1/10 V2 
      domain in keratin dimer formation and the potential consequences of its 
      alteration.
FAU - Terrinoni, Alessandro
AU  - Terrinoni A
AUID- ORCID: 0000-0002-7442-2252
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
FAU - Didona, Biagio
AU  - Didona B
AD  - Center of Dermatological Rare Diseases, IDI-IRCCS, Via dei Monti di Creta, Rome 
      Italy.
FAU - Caporali, Sabrina
AU  - Caporali S
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
FAU - Chillemi, Giovanni
AU  - Chillemi G
AD  - SCAI SuperComputing Applications and Innovation Department, Cineca, Via dei Tizii 
      6, Rome, Italy.
FAU - Lo Surdo, Alessandro
AU  - Lo Surdo A
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
FAU - Paradisi, Mauro
AU  - Paradisi M
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
FAU - Annichiarico-Petruzzelli, Margherita
AU  - Annichiarico-Petruzzelli M
AUID- ORCID: 0000-0002-4717-4740
AD  - Biochemistry Laboratory, IDI-IRCCS, via Monti di Creta, Rome, Italy.
FAU - Candi, Eleonora
AU  - Candi E
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
AD  - Biochemistry Laboratory, IDI-IRCCS, via Monti di Creta, Rome, Italy.
FAU - Bernardini, Sergio
AU  - Bernardini S
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
FAU - Melino, Gerry
AU  - Melino G
AUID- ORCID: 0000-0001-9428-5972
AD  - Department of Experimental Medicine and Biochemical Sciences, University of Rome 
      "Tor Vergata", Rome, Italy.
LA  - eng
GR  - MC_U132670600/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00025/2/MRC_/Medical Research Council/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180424
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (KRT1 protein, human)
RN  - 0 (KRT10 protein, human)
RN  - 0 (Keratin-1)
RN  - 147785-83-9 (Keratin-10)
RN  - Ichthyosis hystrix, Curth Macklin type
SB  - IM
MH  - *Amino Acid Substitution
MH  - Dermatitis, Seborrheic/*genetics
MH  - Female
MH  - Humans
MH  - Ichthyosis/*genetics
MH  - Infant
MH  - Keratin-1/chemistry/*genetics
MH  - Keratin-10/chemistry/*genetics
MH  - Models, Molecular
MH  - Protein Conformation
MH  - Protein Domains
PMC - PMC5918167
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/04/25 06:00
MHDA- 2018/07/22 06:00
PMCR- 2018/04/24
CRDT- 2018/04/25 06:00
PHST- 2017/07/17 00:00 [received]
PHST- 2018/03/29 00:00 [accepted]
PHST- 2018/04/25 06:00 [entrez]
PHST- 2018/04/25 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
PHST- 2018/04/24 00:00 [pmc-release]
AID - PONE-D-17-26735 [pii]
AID - 10.1371/journal.pone.0195792 [doi]
PST - epublish
SO  - PLoS One. 2018 Apr 24;13(4):e0195792. doi: 10.1371/journal.pone.0195792. 
      eCollection 2018.