TY - JOUR
T1 - GNAT1 associated with autosomal recessive congenital stationary night blindness
AU - Naeem, Muhammad Asif
AU - Chavali, Venkata R.M.
AU - Ali, Shahbaz
AU - Iqbal, Muhammad
AU - Riazuddin, Saima
AU - Khan, Shaheen N.
AU - Husnain, Tayyab
AU - Sieving, Paul A.
AU - Ayyagari, Radha
AU - Riazuddin, Sheikh
AU - Fielding Hejtmancik, J.
AU - Amer Riazuddin, S.
PY - 2012/3
Y1 - 2012/3
N2 - PURPOSE Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS. A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS. The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina. CONCLUSIONS. These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.
AB - PURPOSE Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS. A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS. The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina. CONCLUSIONS. These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.
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U2 - 10.1167/iovs.11-8026
DO - 10.1167/iovs.11-8026
M3 - Article
C2 - 22190596
AN - SCOPUS:84861133514
SN - 0146-0404
VL - 53
SP - 1353
EP - 1361
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 3
ER -