Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Association of INVS (NPHP2) mutation in an adolescent exhibiting nephronophthisis (NPH) and complete situs inversus. 1821 8

We report a term female infant born to nonconsanguineous parents who presented with renal failure at birth, hypothyroidism, cholestasis, and progressive cardiac dysfunction. Multigene next-generation sequencing panels for cholestasis, cardiomyopathy, and cystic renal disease did not reveal a unifying diagnosis. Whole exome sequencing revealed compound heterozygous pathogenic variants in ANKS6 (Ankyrin Repeat and Sterile Alpha Motif Domain Containing 6), which encodes a protein that interacts with other proteins of the Inv compartment of cilium (NEK8, NPHP2/INVS, and NPHP3). ANKS6 has been shown to be important for early renal development and cardiac looping in animal models. Autopsy revealed cystic renal dysplasia and cardiomyocyte hypertrophy, disarray, and focal necrosis. Liver histology revealed cholestasis and centrilobular necrosis, which was likely a result of progressive cardiac failure. This is the first report of compound heterozygous variants in ANKS6 leading to a nephronopthisis-related ciliopathy-like phenotype. We conclude that pathogenic variants in ANKS6 may present early in life with severe renal and cardiac failure, similar to subjects with variants in genes encoding other proteins in the Inv compartment of the cilium.
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PMID:Clinical and Pathological Features of a Newborn With Compound Heterozygous ANKS6 Variants. 3163 28