Screening the 3 ' region of the polycystic kidney disease 1 (PKD1) gene in41 Bulgarian and Australian kindreds reveals a prevalance of protein truncating mutations
N. Bogdanova et al., Screening the 3 ' region of the polycystic kidney disease 1 (PKD1) gene in41 Bulgarian and Australian kindreds reveals a prevalance of protein truncating mutations, HUM MUTAT, 16(2), 2000, pp. 166-174
Screening for disease causing mutations in the unique region of the polycys
tic kidney disease 1 (PKD1) gene was performed in 41 unrelated individuals
with autosomal dominant polycystic kidney disease. Exons 34-41 and 43-46 we
re assayed using PCR amplification and SSCP analysis followed by direct seq
uencing of amplicons presenting variant SSCP patterns. We have identified s
even disease-causing mutations of which five are novel [c.10634-10656del; c
.11587delG; IVS37-10C>A; c.11669-11674del; c.13069-13070ins39] and two have
been reported previously [Q4010X; Q4041X]. Defects in this part of the gen
e thus account for 17% of our group of patients. Five of the seven sequence
alterations detected are protein-truncating which is in agree ment with mu
tation screening data for this part of the gene by other groups. The two ot
her mutations are in-frame deletions or insertions which could destroy impo
rtant functional properties of polycystin 1, These findings suggest that th
e first step toward cyst formation in PKD1 patients is the loss of one func
tional copy of polycystin 1, which indirectly supports the "two-hit" model
of cystogenesis where a second somatic mutation inactivating the normal all
ele is necessary to occur for develop ment of the disease condition, Hum Mu
tat 16:166-174, 2000, (C) 2000 Wiley Liss, Inc.