MKS3-Related Ciliopathy with Features of Autosomal Recessive Polycystic Kidney Disease, Nephronophthisis, and Joubert Syndrome

Meral Gunay-Aygun, Melissa A. Parisi, Dan Doherty, Maya Tuchman, Ekaterini Tsilou, David E. Kleiner, Marjan Huizing, Baris Turkbey, Peter Choyke, Lisa Guay-Woodford, Theo Heller, Katarzyna Szymanska, Colin A. Johnson, Ian Glass, William A. Gahl

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To describe 3 children with mutations in a Meckel syndrome gene (MKS3), with features of autosomal recessive polycystic kidney disease (ARPKD), nephronophthisis, and Joubert syndrome (JS). Studydesign: Biochemical evaluations, magnetic resonance and ultrasound imaging, electroretinograms, IQ testing, and sequence analysis of the PKHD1 and MKS3 genes were performed. Functional consequences of the MKS3 mutations were evaluated by cDNA sequencing and transfection studies with constructs of meckelin, the protein product of MKS3. Results: These 3 children with MKS3 mutations had features typical of ARPKD, that is, enlarged, diffusely microcystic kidneys and early-onset severe hypertension. They also exhibited early-onset chronic anemia, a feature of nephronophthisis, and speech and oculomotor apraxia, suggestive of JS. Magnetic resonance imaging of the brain, originally interpreted as normal, revealed midbrain and cerebellar abnormalities in the spectrum of the "molar tooth sign" that characterizes JS. Conclusions: These findings expand the phenotypes associated with MKS3 mutations. MKS3-related ciliopathies should be considered in patients with an ARPKD-like phenotype, especially in the presence of speech and oculomotor apraxia. In such patients, careful expert evaluation of the brain images can be beneficial because the brain malformations can be subtle.

Original languageEnglish (US)
Pages (from-to)386-392.e1
JournalJournal of Pediatrics
Volume155
Issue number3
DOIs
StatePublished - Sep 2009
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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