Polycystic kidney disease
At a minimum, these SNPs are known to be related, and others may also be
Polycystic kidney disease (PKD) is a common inherited disorder. About 600,000 people in the United States have a type of PKD.
There are two forms of PKD: autosomal dominant PKD (ADPKD) and autosomal recessive (ARPKD). ADPKD is far more common than ARPKD.
Autosomal Dominant Polycystic Kidney Disease
Characterized by the development of renal cysts and resulting in end-stage renal disease (ESRD) in about half of all patients by the age of 60, may also involve polycystic liver disease (PLD) as well as an increased risk for intracranial aneurysms. Hypertension is a common early symptom (but there are many other causes of hypertension).
There are currently four genes known to harbor potentially disease-causing ADPKD mutations. In about 75% of patients, (dominant) mutations are found in the PKD1 gene, and in about 15%, mutations are found in the PKD2 gene. Less commonly, ADPKD mutations have been reported in the GANAB and DNAJB11 genes.
Disease progression and prognosis is quite variable, depending on both genetic and non-genetic factors. Genetically, truncating PKD1 mutations are usually associated with earlier onset of ESRD (median age ~58) versus non-truncating (~67 years), while for PKD2 mutations, it's quite later (~78), and for GANAB mutations, ESRD hasn't been observed.
Autosomal Recessive Polycystic Kidney Disease
Autosomal recessive polycystic kidney disease (ARPKD) is much less common, and is normally caused by inheriting two mutations in the PKHD1 gene. Around 1 in 20,000 newborns are born with ARPKD, and about half die soon after birth.
- rs28939383, now merged into rs137852944; OMIM 606702.0001; risk allele A; Thr36Met; the most common missense mutation
- rs28937907; OMIM 606702.0002
- rs28939099; OMIM 606702.0004
Other PKHD1 mutations found in more than one family include (with their 23andMe i-SNP identifiers when known):
- rs369925690; c.664A>G (p.Ile222Val); i5000047
- rs199531851; c.2414C>T (p.Pro805Leu); i5000044 and i6016699
- rs200179145; c.6992T>A (p.Ile2331Lys); i6016629
- rs760222236; c.8870T>C (p.Ile2957Thr); i5000045 and i6016633
- rs200511261; c.9530T>C (p.Ile3177Thr); i5000043 and i6016654
- rs201082169; c.10174C>T (p.Gln3392X); i5000046 and i6016608
- rs746838237; c.5895dupA (p.Leu1966fs); i5012609 most likely
- rs398124502; c. 9689del A. (p.Asp3230fs); i5012610 most likely
- rs398124484; c.3761_3762del insG, (p.Ala1254fs)
- rs137852949; i5012612; more common in Finnish populations
There are also some PKHD1 SNPs considered benign, i.e. not associated or causing PKHD1-based disorders, including: