Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness.
نویسندگان
چکیده
Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway. Mutations in NYX, GRM6, and TRPM1, expressed in the outer plexiform layer (OPL) lead to disruption of the ON-bipolar cell response and have been seen in patients with cCSNB. Whole-exome sequencing in cCSNB patients lacking mutations in the known genes led to the identification of a homozygous missense mutation (c.1807C>T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs(∗)57]) in a simplex male cCSNB patient. Additional screening with Sanger sequencing of 40 patients identified three other cCSNB patients harboring additional allelic mutations in GPR179. Although, immunhistological studies revealed Gpr179 in the OPL in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and Müller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated.
منابع مشابه
Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy
GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying pro...
متن کاملErratum: Molecular profiling of complete congenital stationary night blindness: A pilot study on an Indian cohort
PURPOSE Congenital stationary night blindness (CSNB) is a non-progressive retinal disorder that shows genetic and clinical heterogeneity. CSNB is inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait and shows a good genotype-phenotype correlation. Clinically, CSNB is classified as the Riggs type and the Schubert-Bornschein type. The latter form is further sub-cla...
متن کاملNovel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family
PURPOSE To report the clinical and genetic findings of one family with autosomal recessive cone dystrophy (CD) and to identify the causative mutation. METHODS An institutional study of three family members from two generations. The clinical examination included best-corrected Snellen visual acuity measurement, fundoscopy, the Farnsworth D-15 color vision test, a full-field electroretinogram (...
متن کاملMutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness
PURPOSE This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families. METHODS Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, inclu...
متن کاملWhole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family
Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant‑like USH family in successive generations was identified, and the present study aimed to determ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of human genetics
دوره 90 2 شماره
صفحات -
تاریخ انتشار 2012