A novel mutation in pkhd1 gene in an Iranian family with an abortion affected with Autosomal Recessive polycystic kidney disease

Polycystic kidney disease (PKD) is a genetic disorder in which abnormal cysts develop and grow in the kidneys. Cystic disorders can express themselves at any point, infancy, childhood, or adulthood. PKD is characterized by the presence of multiple cysts typically in both kidneys; however, 17% of cases initially present with observable disease in one kidney, with most cases progressing to bilateral disease in adulthood. The two types of PKD are autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ARPKD is the lesser common type and the incidence of ARPKD is estimated at 1:10,000 to 1:40,000. The majority of individuals with autosomal recessive polycystic kidney disease (ARPKD) present in the neonatal period with enlarged echogenic kidneys. Mutations in the PKHD1 on chromosome 6p12.2 cause ARPKD. Symptoms and signs include abdominal discomfort, polyuria, polydipsia, incidental discovery of hypertension, and abdominal mass. At initial presentation, approximately 45% of infants have liver abnormalities. With neonatal respiratory support and renal replacement therapies, the ten-year survival of those who live beyond the first year of life has improved to 82%. A minority present in older childhood or young adulthood with hepatosplenomegaly and evidence of portal hypertension. The classic presentation for ARPKD is systemic hypertension with progression to end-stage renal disease (ESRD) by the age of 15. : This study includes a couple who their child was aborted due to PKD. PKHD1 gene was analyzed in father by NGS method, and the mutation found in the father was analyzed in the mother by Sanger sequencing.A possible pathogenic mutation, c.6469C> T (p.Gln2157Ter), on PKHD1 (NM_138694) gene was detected in parents both Although there is no report that this mutation is ever identified in PKHD1 gene in ARPKD patients, the early termination of amino acid production is expected to affect the protein’s function as a possible pathogenic mutation in a heterozygous state. Although there is no report that this mutation is ever identified in PKHD1 gene in ARPKD patients, the early termination of amino acid production is expected to affect the protein’s function as a possible pathogenic mutation.

Keywords:

polycystic Kidney disease , PKHD1 , cystic disorder , ARPKD