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Case Report
Autosomal Recessive Polycystic Kidney Disease
Family 54
ARPKD is characterized by the presence of multiple cysts (hence, "polycystic") in both kidneys .
Clinical presentation can often be noted before birth by ultrasound.
Affected newborn infants have a distended abdomen due to grossly enlarged kidneys.
There is a wide clinical presentation involving the liver, pancreas, and rarely, the heart and brain
PKHD1 is the only gene known to be associated with the wide clinical spectrum of ARPKD.
Localised to chromosome 6p21.1-p12 PKHD1 is 470KB in length It is a large gene -67 exons in the longest open
reading frame No common mutations
(Bergmann et al 2005) 276 pathogenic mutations identified on 670 mutated alleles
Polycystic Kidney and Hepatic Disease 1
51Mb 52Mb 53Mb 54Mb
0Mb 107Mb51Mb
p12.3 p12.2 p12.1
D6S436 D6S465D6S1714
D6S1573
D6S466
PKHD1
p12
D6S243
3’ 5’
Intron 60
Chromosome 6
Family referred for future prenatal diagnosis
6M0685AH
4/4/1971
6M0686JH
4/6/1973
6M0336BH
15/6/2005
Flanking and intragenic marker panel
Linkage D6S 436 3’ (sometimes excluded)
D6S 465 3’
D6S 1714 intragenic
D6S 243 intragenic intron 60
D6S 1573 5’
D6S466 5’
Sequencing progress
PKHD1 has 67 exons
Sequencing identified the paternal mutation
c.107C>CT[p.T36M]
Maternal mutation unidentified
Haplotypes for markers
6M0685AH
4/4/1971(194) (?)
129 125218 218
Affected Normal259 261105 111
6M0686JH
4/6/1973182 184125 125224 226
Normal Affected259 255105 109
6M0336BH
15/6/2005194 184129 125218 226
Affected Affected259 255105 109
Fetus referred for prenatal diagnosis
6M0685AH
4/4/1971(194) (?)
129 125218 218
Affected Normal259 261105 111
6M0686JH
4/6/1973182 184125 125224 226
Normal Affected259 255105 109
6M0336BH
15/6/2005194 184129 125218 226
Affected Affected259 255105 109
Markers D6S243 and D6S1714are intragenic.
Recombination identified
6M0685AH
4/4/1971(194) (?)
129 125218 218
Affected Normal259 261105 111
6M0686JH
4/6/1973182 184125 125224 226
Normal Affected259 255105 109
6M0336BH
15/6/2005194 184129 125218 226
Affected Affected259 255105 109
8M0857Fetus 1
194 184129 125218 226
Affected ?259 259105 105
Markers D6S243 and D6S1714are intragenic.
Order of individuals of genescan Affected child Father Mother Fetus
D6S1714 D6S243
D6S1573 D6S466
Polycystic Kidney and Hepatic Disease 1
51Mb 52Mb 53Mb 54Mb
0Mb 107Mb51Mb
p12.3 p12.2 p12.1
D6S436 D6S465D6S1714
D6S1573
D6S466
PKHD1
p12
D6S243
3’ 5’
Intron 60
Chromosome 6
Location of X over
Look at other SNP’s within the gene towards the 5’ end
Exon 4 c.234C>CT [p.D78D] Intron4 c.282-41A>AG Intron 7 c.527+19C>CT Exon 22 c.2278C>CT[p.R60R] Exon 32.1 c.3785C>CT[p.A1262V] Intron 48 c. 7733+33C>CT
6M0685AH
4/4/1971T36M Normal
A GC TC T
MutationExon5Exon7
Exon22
6M0686JH
4/6/1973Normal Unknown
A GC TC T
6M0336BH
15/6/2005T36M Unknown
?A/G??C/T??C/T?
MutationExon5Exon7
Exon22
8M0857Fetus
T36M Unknown?A/G??C/T??C/T?
Mutations and SNP analysisExons 5, 7, 22
