New mutations in the transglutaminase 1 gene in three families with lamellar ichthyosis.
BACKGROUND
Autosomal recessive lamellar ichthyosis (LI) is a severe skin disorder characterized by generalized hyperkeratosis. Gene mutation in transglutaminase 1 (TGM1), which mediates cross-links in the formation of the cell envelope during terminal differentiation of epidermis, has been identified as a cause of LI.


OBJECTIVE
To determine mutations of TGM1 gene in three Chinese families with LI.


METHODS
The TGM1 gene was sequenced to identify disease-causing mutations in the three families with LI. One of the results was confirmed by using reverse transcriptase PCR and in situ hybridization. An in situ transglutaminase (TGase) 1 assay was performed to estimate TGase 1 activity in the patients' skin.


RESULTS
Four novel mutations of keratinocyte TGase1 (Q203X, D254N, R687H and IVS4 + 1G-->T) were found in the three families. No TGase 1 mRNA was detected in patient skin using RT-PCR and in situ hybridization, and the in situ TGase assay showed that there was no or decreased TGase 1 activity in patient skin.


CONCLUSIONS
Our findings suggest that four novel mutations in TGM1 gene result in decrease or absence of TGase activity in the skin and, as a consequence, cause the phenotype of LI.
Cao
X
X
Department of Dermatology, First Affiliated Hospital of Nan Chang University, Nan Chang, China.
Lin
Z
Z
Yang
H
H
Bu
D
D
Tu
P
P
Chen
L
L
Wu
H
H
Yang
Y
Y
D000328:Adult; D002648:Child; D003241:Consanguinity; D005838:Genotype; D006801:Humans; D017490:Ichthyosis, Lamellar / Q000235:genetics*; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics*
D012333:RNA, Messenger; D011503:Transglutaminases; C105804:transglutaminase 1