NPHP3 mutations are associated with neonatal onset multiorgan polycystic disease in two siblings.
Two siblings with a severe multiorgan polycystic disease presenting in the neonatal period were identified. Their genetic testing identified compound heterozygous NPHP3 gene mutations, parents being heterozygous carriers. The mutations included a splice-site (c.958-2A>G) and a missense mutation (c.2342G>A; p.G781D), both being extremely rare. NPHP3 encodes for nephrocystin 3 present on the cilia-centrosome complex. We hypothesize that these mutations lead to defective cilia-based signaling, required for normal development of the renal, pancreatic, biliary and portal system. This report outlines a rare neonatal ciliopathy presentation of NPHP3 mutations leading to severe multiorgan failure in two siblings.
1] Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [2] Harvard Stem Cell Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [3] The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Leeman
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Dobson
1] The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [2] Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Towne
Division of Neonatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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Dukhovny
1] Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [2] The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [3] Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Joshi
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Stoler
1] Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [2] The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA [3] Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
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Agrawal
D000328:Adult; D003560:Cysts / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation
C528697:nephrocystin-3, human; D016547:Kinesins