TY - JOUR
T1 - A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness
AU - Riazuddin, S. Amer
AU - Shahzadi, Amber
AU - Zeitz, Christina
AU - Ahmed, Zubair M.
AU - Ayyagari, Radha
AU - Chavali, Venkata R.M.
AU - Ponferrada, Virgilio G.
AU - Audo, Isabelle
AU - Michiels, Christelle
AU - Lancelot, Marie Elise
AU - Nasir, Idrees A.
AU - Zafar, Ahmad U.
AU - Khan, Shaheen N.
AU - Husnain, Tayyab
AU - Jiao, Xiaodong
AU - MacDonald, Ian M.
AU - Riazuddin, Sheikh
AU - Sieving, Paul A.
AU - Katsanis, Nicholas
AU - Hejtmancik, J. Fielding
N1 - Funding Information:
The authors are grateful to all family members for their participation in this study. None of the contributing authors have any financial interest related to this work. This work was supported in part by Higher Education Commission (H.E.C.), Islamabad, Pakistan; Ministry of Science and Technology, Islamabad, Pakistan; NIH-R00-DC009287-03 (Z.A.); Research to Prevent Blindness (Z.A.); Foundation Fighting Blindness, USA (R.A.), Research to prevent blindness (R.A.) and NIH-EY013198 (R.A.). N.K. is a Distinguished George W. Brumley Professor.
PY - 2010/10/8
Y1 - 2010/10/8
N2 - Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder that can be associated with impaired night vision. The last decade has witnessed huge progress in ophthalmic genetics, including the identification of three genes implicated in the pathogenicity of autosomal-recessive CSNB. However, not all patients studied could be associated with mutations in these genes and thus other genes certainly underlie this disorder. Here, we report a large multigeneration family with five affected individuals manifesting symptoms of night blindness. A genome-wide scan localized the disease interval to chromosome 15q, and recombination events in affected individuals refined the critical interval to a 10.41 cM (6.53 Mb) region that harbors SLC24A1, a member of the solute carrier protein superfamily. Sequencing of all the coding exons identified a 2 bp deletion in exon 2: c.1613-1614del, which is predicted to result in a frame shift that leads to premature termination of SLC24A1 (p.F538CfsX23) and segregates with the disorder under an autosomal-recessive model. Expression analysis using mouse ocular tissues shows that Slc24a1 is expressed in the retina around postnatal day 7. In situ and immunohistological studies localized both SLC24A1 and Slc24a1 to the inner segment, outer and inner nuclear layers, and ganglion cells of the retina, respectively. Our data expand the genetic basis of CSNB and highlight the indispensible function of SLC24A1 in retinal function and/or maintenance in humans.
AB - Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder that can be associated with impaired night vision. The last decade has witnessed huge progress in ophthalmic genetics, including the identification of three genes implicated in the pathogenicity of autosomal-recessive CSNB. However, not all patients studied could be associated with mutations in these genes and thus other genes certainly underlie this disorder. Here, we report a large multigeneration family with five affected individuals manifesting symptoms of night blindness. A genome-wide scan localized the disease interval to chromosome 15q, and recombination events in affected individuals refined the critical interval to a 10.41 cM (6.53 Mb) region that harbors SLC24A1, a member of the solute carrier protein superfamily. Sequencing of all the coding exons identified a 2 bp deletion in exon 2: c.1613-1614del, which is predicted to result in a frame shift that leads to premature termination of SLC24A1 (p.F538CfsX23) and segregates with the disorder under an autosomal-recessive model. Expression analysis using mouse ocular tissues shows that Slc24a1 is expressed in the retina around postnatal day 7. In situ and immunohistological studies localized both SLC24A1 and Slc24a1 to the inner segment, outer and inner nuclear layers, and ganglion cells of the retina, respectively. Our data expand the genetic basis of CSNB and highlight the indispensible function of SLC24A1 in retinal function and/or maintenance in humans.
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U2 - 10.1016/j.ajhg.2010.08.013
DO - 10.1016/j.ajhg.2010.08.013
M3 - Article
C2 - 20850105
AN - SCOPUS:77957755097
SN - 0002-9297
VL - 87
SP - 523
EP - 531
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -