1. Case Report Autosomal Recessive Polycystic Kidney Disease Family 54

2. 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

3. 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

4. Polycystic Kidney and Hepatic Disease 1 51Mb 52Mb 53Mb54Mb 0Mb 107Mb51Mb p12.3p12.2 p12.1 D6S436D6S465 D6S1714 D6S1573 D6S466 PKHD1 p12 D6S243 3’ 5’ Intron 60 Chromosome 6

5. Family referred for future prenatal diagnosis

6. 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’

7. Sequencing progress PKHD1 has 67 exons Sequencing identified the paternal mutation c.107C>CT[p.T36M] Maternal mutation unidentified

8. Haplotypes for markers

9. Fetus referred for prenatal diagnosis

10. Recombination identified

11. Order of individuals of genescan Affected child Father Mother Fetus

12. D6S1714 D6S243

13. D6S1573 D6S466

14. Polycystic Kidney and Hepatic Disease 1 51Mb 52Mb 53Mb54Mb 0Mb 107Mb51Mb p12.3p12.2 p12.1 D6S436D6S465 D6S1714 D6S1573 D6S466 PKHD1 p12 D6S243 3’ 5’ Intron 60 Chromosome 6

15. 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 32.1c.3785C>CT[p.A1262V] Intron 48c. 7733+33C>CT