Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:2.7.7.49 (
reverse transcriptase
)
31,746
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hailey-Hailey disease
(
HHD
) is genetic skin disorder characterized by repeated and exacerbated skin lesions in friction regions.
ATP2C1
, encoding SPCA1, was demonstrated to be the responsible gene for
HHD
pathogenesis. However, for some cases, no
ATP2C1
mutation could be determined by standard Sanger sequencing, thereby obscuring the cause and diagnosis of
HHD
. In this study, we investigated the possibility that
HHD
is caused by complex
ATP2C1
defects using multiplex ligation-dependent probe amplification (MLPA) analysis for 10 of 50 cases in our institute without
ATP2C1
mutations. In one female Japanese patient and her father, who also show
HHD
, MLPA followed by polymerase chain reaction (PCR) analyses revealed a novel duplication of exons 8-16 of
ATP2C1
. The duplication was predicted to add 20,615 base pairs, 882 nt, and 294-amino-acid residues to the genome, mRNA and SPCA1 protein, respectively. By
reverse transcriptase
-PCR using patient skin RNA, we could confirm that a larger transcript was produced and we found that the abundance of the normal transcript was clearly reduced in the patient. Putative structures of wild-type and duplicated proteins revealed differences in arrangement of SPCA1 domains that may have functional consequences. Strikingly, the phosphorylation and the nucleotide-binding domains were interrupted by insertion of a partial actuator, transmembrane, and phosphorylation domains. The additional 294 amino acids appear to disrupt SPCA1 structure and function, causing
HHD
. Our study expands the spectrum of genetic defects in
HHD
and showed that disruption of SPCA1 structure and function by the microduplication caused
HHD
in the patient and her father.
...
PMID:A Novel Microduplication Spanning Exons 8-16 of
ATP2C1
That Was Undetectable by Standard Sanger Sequencing in a Japanese Patient With Hailey-Hailey Disease. 3301 87
