Association of INVS (NPHP2) mutation in an adolescent exhibiting nephronophthisis (NPH) and complete situs inversus

Cystic kidney disease has been linked to mutations in the Invs gene in mice with an inversion of embryonic turning (inv/inv) and the INVS (NPHP2) gene in human infantile nephronophthisis (NPH). Infantile NPH shows marked cyst formation in contrast to other forms of NPH and rapidly progresses to end-stage renal failure (ESRD) before 5 years of age. In this report, we describe an adolescent with a mutation in INVS who had preservation of his renal function beyond infancy. The patient showed findings of NPH with mild renal insufficiency together with situs inversus. He also exhibited a series of features consistent with Jeune syndrome involving asphyxiating thoracic dystrophy, heart failure and hypertension prior to advanced renal insufficiency. Based upon these features, our patient is likely to have the combined clinical features of infantile NPH with Jeune syndrome. Genetic analysis for INVS disclosed a heterozygous mutation of TrG at position rs7024375 in the 5'UTR of INVS in the patient and his mother, while no abnormalities were found in any of the 17 exons of INVS or NPHP1, 3 and 4. To our knowledge, this is the first patient possessing a genetic alteration in INVS who had preservation of renal function past childhood. This study suggests that our patient may be a compound heterozygote for infantile NPH and Jeune syndrome, because both these disorders are transmitted mainly as an autosomal-recessive trait.