Journal article
Authors list: Zaki, Maha S.; Heller, Raoul; Thoenes, Michaela; Nuernberg, Gudrun; Stern-Schneider, Gabi; Nuernberg, Peter; Karnati, Srikanth; Swan, Daniel; Fateen, Ekram; Nagel-Wolfrum, Kerstin; Mostafa, Mostafa I.; Thiele, Holger; Wolfrum, Uwe; Baumgart-Vogt, Eveline; Bolz, Hanno J.
Publication year: 2016
Pages: 170-174
Journal: Human Mutation: Variation, Informatics and Disease
Volume number: 37
Issue number: 2
ISSN: 1059-7794
eISSN: 1098-1004
Open access status: Gold
DOI Link: https://doi.org/10.1002/humu.22934
Publisher: Wiley
Abstract:
Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent. Genome-wide homozygosity mapping and whole-exome sequencing detected a homozygous missense mutation, c.1238G>T (p.Gly413Val), affecting a highly conserved residue of peroxisomal biogenesis factor 6, PEX6. Biochemical profiling of the siblings revealed abnormal and borderline plasma phytanic acid concentration, and cerebral imaging revealed white matter disease in both. We show that Pex6 localizes to the apical extensions of secretory ameloblasts and differentiated odontoblasts at early stages of dentin synthesis in mice, and to cilia of retinal photoreceptor cells. We propose PEX6, and possibly other peroxisomal genes, as candidate for the rare cooccurrence of deafblindness and enamel dysplasia. Our study for the first time links peroxisome biogenesis disorders to retinal ciliopathies. (C) 2015 Wiley Periodicals, Inc.
Citation Styles
Harvard Citation style: Zaki, M., Heller, R., Thoenes, M., Nuernberg, G., Stern-Schneider, G., Nuernberg, P., et al. (2016) PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly, Human Mutation: Variation, Informatics and Disease, 37(2), pp. 170-174. https://doi.org/10.1002/humu.22934
APA Citation style: Zaki, M., Heller, R., Thoenes, M., Nuernberg, G., Stern-Schneider, G., Nuernberg, P., Karnati, S., Swan, D., Fateen, E., Nagel-Wolfrum, K., Mostafa, M., Thiele, H., Wolfrum, U., Baumgart-Vogt, E., & Bolz, H. (2016). PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly. Human Mutation: Variation, Informatics and Disease. 37(2), 170-174. https://doi.org/10.1002/humu.22934
Keywords
ADULT REFSUM-DISEASE; CONNECTING CILIUM; deafblindness; enamel dysplasia; peroxisome biogenesis disorders; PEROXISOME BIOGENESIS DISORDERS; PEX6; retinal ciliopathy; Retinal degeneration; USHER-SYNDROME
