TY - JOUR
T1 - Molecular analysis of a consanguineous Iranian polycystic kidney disease family identifies a PKD2 mutation that aids diagnostics
AU - Vazifehmand, Reza
AU - Rossetti, Sandro
AU - Saber, Sassan
AU - Khorshid, Hamid Reza Khorram
AU - Harris, Peter C.
N1 - Funding Information:
We wish to thank all the family members and clinicians who participated in this study. This work was supported by NIDDK grant DK058816 and the Mayo Clinic PKD Translational Center (DK090728).
PY - 2013
Y1 - 2013
N2 - Background: Polycystic kidney diseases (PKD) are a group of monogenic disorders that are inherited dominantly (autosomal dominant PKD; ADPKD) or recessively, including, autosomal recessive PKD (ARPKD). A number of recessive, syndromic disorders also involve PKD but have a range of pleiotropic phenotypes beyond the kidney, and are enriched in consanguineous families. Case presentation. We describe here a consanguineous Iranian pedigree in which PKD was diagnosed in four generations, but also included cases with additional abnormalities, including mental retardation. We employed molecular screening to reveal the etiology of the PKD. Since the PKD seemed to be dominantly inherited, molecular diagnostics was performed by direct sequencing of the ADPKD genes, PKD1 and PKD2. Clinical and imaging data was collected on family members. The sequence analysis revealed a PKD2 single base-pair deletion, c.1142delG, and segregation was demonstrated in 16 PKD patients from different branches of the family. In keeping with other reports, the PKD2 phenotype in this family was overall mild, and characterized by conserved kidney function, although 12 cases had some evidence of renal insufficiency. Several younger mutation carriers had borderline or no clinical characteristics of ADPKD, while a patient that required a renal transplant at 14 y did not have the PKD2 mutation. Conclusions: The molecular analysis of an Iranian family showed that the PKD was due to a PKD2 mutation. The identification of the causative mutation allowed an accurate diagnosis in a number of individuals with equivocal imaging data. Consequently, these patients could be followed appropriately as at-risk individuals. In addition, the PKD2 diagnosis ruled out a syndromic form of PKD as the cause of the additional phenotypes in the family.
AB - Background: Polycystic kidney diseases (PKD) are a group of monogenic disorders that are inherited dominantly (autosomal dominant PKD; ADPKD) or recessively, including, autosomal recessive PKD (ARPKD). A number of recessive, syndromic disorders also involve PKD but have a range of pleiotropic phenotypes beyond the kidney, and are enriched in consanguineous families. Case presentation. We describe here a consanguineous Iranian pedigree in which PKD was diagnosed in four generations, but also included cases with additional abnormalities, including mental retardation. We employed molecular screening to reveal the etiology of the PKD. Since the PKD seemed to be dominantly inherited, molecular diagnostics was performed by direct sequencing of the ADPKD genes, PKD1 and PKD2. Clinical and imaging data was collected on family members. The sequence analysis revealed a PKD2 single base-pair deletion, c.1142delG, and segregation was demonstrated in 16 PKD patients from different branches of the family. In keeping with other reports, the PKD2 phenotype in this family was overall mild, and characterized by conserved kidney function, although 12 cases had some evidence of renal insufficiency. Several younger mutation carriers had borderline or no clinical characteristics of ADPKD, while a patient that required a renal transplant at 14 y did not have the PKD2 mutation. Conclusions: The molecular analysis of an Iranian family showed that the PKD was due to a PKD2 mutation. The identification of the causative mutation allowed an accurate diagnosis in a number of individuals with equivocal imaging data. Consequently, these patients could be followed appropriately as at-risk individuals. In addition, the PKD2 diagnosis ruled out a syndromic form of PKD as the cause of the additional phenotypes in the family.
KW - ADPKD
KW - Molecular diagnostics
KW - PKD2
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U2 - 10.1186/1471-2369-14-190
DO - 10.1186/1471-2369-14-190
M3 - Article
C2 - 24011172
AN - SCOPUS:84883542098
SN - 1471-2369
VL - 14
JO - BMC Nephrology
JF - BMC Nephrology
IS - 1
M1 - 190
ER -