Views: 1,301 | Downloads:
21
| Responses: 0
| XML | Respond to this article | Alert & updates | Request permissions | Email to a friend |
Original ArticleOpen Access
Molecular Defect of PKDJ Gene Resulting in Abnormal RNA Processing in a Thai Family
Rungroj N 
,
Thongnoppakhun W ,
Vareesangthip K ,
Sirinavin C ,
Wilairat P ,
Yenchitsomanus P
,
Thongnoppakhun W ,
Vareesangthip K ,
Sirinavin C ,
Wilairat P ,
Yenchitsomanus P WANNA THONGNOPPAKHUN, Ph.D.*,
CHINTANA SIRINAVIN, M.D.*,***,
PA-THAI YENCHITSOMANUS, Ph.D.*,*****
Autosomal dominant polycystic kidney disease (ADPKD) is a common human autosomal
disorder caused mainly by mutations of the
PKDJ
gene. In analysis of
PKDJ
transcripts by long
RT-PCR and nested PCR procedures, we observed
PKDJ-cDNA
fragments from three ADPKD
siblings from the same family with a size approximately 250 base pairs (bp) shorter than normal.
Further investigations showed that the
PKDJ
transcripts from these patients had been abnormally
processed, the nucleotide sequence of exon 43 containing 291 nt was missing from the transcripts,
which would result in an abnormal polycystin-1 with an in-frame deletion of 97 amino acids. This
splicing defect did not result from a mutation that disrupted the splice donor or acceptor sites
adjacent to exon 43 or the branch sites in flanking introns but was most likely due to 20-bp
deletion observed in intron 43. The intronic deletion was present in 8 affected members but absent
in 11 unaffected members, corresponding with the results of genetic linkage analysis using 5
polymorphic markers in the
PKDJ
region. Molecular diagnosis of
PKDJ
in this family could,
therefore, be carried out by genomic DNA amplification to directly detect the
PKDJ
intronic
deletion.
Key word:
Polycystic Kidney Disease 1
(PKDJ), PKDJ
Mutation, Intronic Deletion, Exon Skipping,
RNA Processing Defect, Abnormal Splicing
CHINTANA SIRINAVIN, M.D.*,***,
PA-THAI YENCHITSOMANUS, Ph.D.*,*****
Autosomal dominant polycystic kidney disease (ADPKD) is a common human autosomal
disorder caused mainly by mutations of the
PKDJ
gene. In analysis of
PKDJ
transcripts by long
RT-PCR and nested PCR procedures, we observed
PKDJ-cDNA
fragments from three ADPKD
siblings from the same family with a size approximately 250 base pairs (bp) shorter than normal.
Further investigations showed that the
PKDJ
transcripts from these patients had been abnormally
processed, the nucleotide sequence of exon 43 containing 291 nt was missing from the transcripts,
which would result in an abnormal polycystin-1 with an in-frame deletion of 97 amino acids. This
splicing defect did not result from a mutation that disrupted the splice donor or acceptor sites
adjacent to exon 43 or the branch sites in flanking introns but was most likely due to 20-bp
deletion observed in intron 43. The intronic deletion was present in 8 affected members but absent
in 11 unaffected members, corresponding with the results of genetic linkage analysis using 5
polymorphic markers in the
PKDJ
region. Molecular diagnosis of
PKDJ
in this family could,
therefore, be carried out by genomic DNA amplification to directly detect the
PKDJ
intronic
deletion.
Key word:
Polycystic Kidney Disease 1
(PKDJ), PKDJ
Mutation, Intronic Deletion, Exon Skipping,
RNA Processing Defect, Abnormal Splicing
Download:
PDF