A mutation in SLC24A1 implicated in autosomal-recessive congenital stationary night blindness.
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.
Riazuddin
S Amer
SA
National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan. riazuddin@ncemb.org
Shahzadi
Amber
A
Zeitz
Christina
C
Ahmed
Zubair M
ZM
Ayyagari
Radha
R
Chavali
Venkata R M
VR
Ponferrada
Virgilio G
VG
Audo
Isabelle
I
Michiels
Christelle
C
Lancelot
Marie-Elise
ME
Nasir
Idrees A
IA
Zafar
Ahmad U
AU
Khan
Shaheen N
SN
Husnain
Tayyab
T
Jiao
Xiaodong
X
MacDonald
Ian M
IM
Riazuddin
Sheikh
S
Sieving
Paul A
PA
Katsanis
Nicholas
N
Hejtmancik
J Fielding
JF
D000818:Animals; D001483:Base Sequence; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009755:Night Blindness / Q000235:genetics*; D012160:Retina / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D019831:Sodium-Calcium Exchanger / Q000235:genetics* / Q000378:metabolism
D019831:Sodium-Calcium Exchanger; C074530:potassium-dependent sodium-calcium exchanger