title: Broadening the ciliopathy spectrum: motile cilia dyskinesia, and nephronophthisis associated with a previously unreported homozygous mutation in the INVS/NPHP2 gene.
abstract: Nephronophthisis associated ciliopathies (NPHP-AC) are a group of phenotypically related conditions that include Joubert syndrome, Meckel syndrome, nephronophthisis (NPHP), and Senior-Loken syndrome. We report on a male fetus with prenatal ultrasound findings at 24 weeks of gestation of anhydramnios, large and echogenic kidneys and situs inversus totalis. Histopathology revealed nephronophthisis and tracheal mucosa electron microscopy revealed ciliary dysgenesis. DNA analysis of the NPHP genes showed a previously unreported homozygous mutation, p.Arg603* (c.1078+1G>A), in the INVS/NPHP2 gene. This mutation is thought to abolish the splice donor site for exon 8, which likely disrupts the normal splicing of the INVS/NPHP2 gene.
authors.affiliation: Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Moalem
authors.forename: Sarah
authors.initials: S
authors.lastname: Keating
authors.forename: Patrick
authors.initials: P
authors.lastname: Shannon
authors.forename: Megan
authors.initials: M
authors.lastname: Thompson
authors.forename: Kathryn
authors.initials: K
authors.lastname: Millar
authors.forename: Keith
authors.initials: K
authors.lastname: Nykamp
authors.forename: Adam
authors.initials: A
authors.lastname: Forster
authors.forename: Abdul
authors.initials: A
authors.lastname: Noor
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
mesh_terms: D002923:Cilia / Q000473:pathology*; D005260:Female; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology; D052177:Kidney Diseases, Cystic / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D009154:Mutation; D011247:Pregnancy; D022821:RNA Splice Sites; D020545:Respiratory Mucosa / Q000473:pathology; D012857:Situs Inversus / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D016216:Ultrasonography, Prenatal
chemical_list: C114503:INVS protein, human; D022821:RNA Splice Sites; D014157:Transcription Factors