Two novel de novo mutations of KRT6A and KRT16 genes in two Chinese pachyonychia congenita pedigrees with fissured tongue or diffuse plantar keratoderma.
BACKGROUND
Mutations in the KRT6A or KRT16 gene cause pachyonychia congenita type 1 (PC-1), while mutations in KRT16 or KRT6C underlie focal palmoplantar keratoderma (FPPK). A new classification system of PC has been adopted based on the mutated gene. PC rarely presents the symptoms of diffuse plantar keratoderma. Mutation in the tail domain of keratins is rarely reported. PC combined with fissured tongue has never been described.


OBJECTIVE
To investigate the genotype-phenotype correlations between clinical features and gene mutational sites in two unrelated southern Chinese PC pedigrees (one family presented with specific fissured tongue, the other with diffuse plantar keratoderma).


METHODS
The whole coding regions of the KRT6A/KRT16/KRT17/KRT6B genes were amplified and directly sequenced to detect the mutation. To confirm the effect of the IVS8-2A>C mutation in KRT6A at the mRNA level, total RNA from the plantar lesion of a patient was extracted and reverse-transcribed to cDNA for sequence analysis.


RESULTS
Two novel de novo mutations, a splice acceptor site variant IVS8-2A>C (p.S487FfsX72) in KRT6A and a heterozygous substitution c.AA373_374GG (p.N125G) within exon 1 of KRT16, were found separately in the two PC families.


CONCLUSIONS
Genotype-phenotype correlations among PC patients with codon-125 mutation in KRT16 were established, while the phenotypes caused by the IVS8-2A>C mutation in KRT6A need further studies to confirm the rare feature of fissured tongue.
Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Women's Hospital, 866 Yuhangtang Road, Hangzhou 310058, China.
Zhen-Fang
ZF
Du
Chen-Ming
CM
Xu
Yan
Y
Zhao
Wen-Ting
WT
Liu
Xiao-Ling
XL
Chen
Chun-Yue
CY
Chen
Hong
H
Fang
Hai-Ping
HP
Ke
Xian-Ning
XN
Zhang
D000328:Adult; D044466:Asian People / Q000235:genetics; D005260:Female; D006801:Humans; D053536:Keratin-16 / Q000235:genetics*; D053553:Keratin-6 / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000150:complications / Q000235:genetics*; D009154:Mutation; D053549:Pachyonychia Congenita / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014063:Tongue, Fissured / Q000150:complications / Q000235:genetics*
D053536:Keratin-16; D053553:Keratin-6