Identification of a Novel Mutation in the CDHR1 Gene in a Family With Recessive Retinal Degeneration

被引:42
作者
Duncan, Jacque L. [5 ]
Roorda, Austin [4 ]
Navani, Mili
Vishweswaraiah, Sangeetha
Syed, Reema [5 ]
Soudry, Shiri [5 ]
Ratnam, Kavitha [5 ]
Gudiseva, Harini V.
Lee, Pauline [3 ]
Gaasterland, Terry [2 ]
Ayyagari, Radha [1 ]
机构
[1] Univ Calif San Diego, Shiley Eye Ctr, Jacobs Retina Ctr, San Diego, CA 92093 USA
[2] Univ Calif San Diego, Inst Genom Med, San Diego, CA 92093 USA
[3] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[4] Univ Calif Berkeley, Sch Optometry, Vis Sci Grad Grp, Berkeley, CA USA
[5] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA
关键词
RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; ADAPTIVE OPTICS; OUTER SEGMENT; PANEL D-15; DYSTROPHY; CADHERIN; DISEASE;
D O I
10.1001/archophthalmol.2012.1906
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Objectives: To describe the clinical phenotype and identify the molecular basis of disease in a consanguineous family of Palestinian origin with autosomal recessive retinal degeneration. Methods: Eight family members were evaluated with visual acuity and perimetry tests, color fundus photographs, full-field electroretinography, and optical coherence tomography. Cone photoreceptors surrounding the fovea were imaged in 2 members, using adaptive optics scanning laser ophthalmoscopy. Exome was captured using probes and sequenced. Readings were mapped to reference hg19. Variant calls and annotations were performed, using published protocols. Confirmation of variants and segregation analysis was performed using dideoxy sequencing. Results: Analysis detected 24 037 single-nucleotide variants in one affected family member, of which 3622 were rare and potentially damaging to encoded proteins. Further analysis revealed a novel homozygous nonsense change, c.1381 C>T, p.Gln461X in exon 13 of the CDHR1 gene, which segregated with retinal degeneration in this family. Affected members had night blindness beginning during adolescence with progressive visual acuity and field loss and unmeasurable electroretinographic responses, as well as macular outer retinal loss, although residual cones with increased cone spacing were observed in the youngest individual. Conclusions: Exome analysis revealed a novel CDHR1 nonsense mutation segregating with progressive retinal degeneration causing severe central vision loss by the fourth decade of life. High-resolution retinal imaging revealed outer retinal changes suggesting that CDHR1 is important for normal photoreceptor structure and survival. Clinical Relevance: Exome sequencing is a powerful technique that may identify causative genetic variants in families with autosomal recessive retinal degeneration. Arch Ophthalmol. 2012; 130(10):1301-1308
引用
收藏
页码:1301 / 1308
页数:8
相关论文
共 50 条
  • [21] Autosomal recessive hypophosphatemic rickets type 2; a novel mutation in the ENPP1 gene
    Bitkin, Eda Celebi
    Aymelek, Huri Sema
    TURKISH JOURNAL OF PEDIATRICS, 2022, 64 (03) : 585 - 591
  • [22] Report of a Novel Mutation in CRB1 in a Lebanese Family Presenting Retinal Dystrophy
    Jalkh, Nadine
    Guissart, Claire
    Chouery, Eliane
    Yammine, Tony
    El Ali, Nagham
    Farah, Hanane Abi
    Megarbane, Andre
    OPHTHALMIC GENETICS, 2014, 35 (01) : 57 - 62
  • [23] Identification of a novel mutation in MEF2C gene in an atypical patient with frontotemporal lobar degeneration
    Adriao, Andreia
    Santana, Isabel
    Ribeiro, Carolina
    Cancela, M. Leonor
    Conceicao, Natercia
    Grazina, Manuela
    NEUROLOGICAL SCIENCES, 2022, 43 (01) : 319 - 326
  • [24] AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration
    Li, David
    Jin, Chongfei
    Jiao, Xiaodong
    Li, Lin
    Bushra, Tahmina
    Naeem, Muhammad Asif
    Butt, Nadeem H.
    Husnain, Tayyab
    Sieving, Paul A.
    Riazuddin, Sheikh
    Riazuddin, S. Amer
    Hejtmancik, J. Fielding
    MOLECULAR VISION, 2014, 20 : 1 - 14
  • [25] Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans
    Zangerl, Barbara
    Goldstein, Orly
    Philp, Alisdair R.
    Lindauer, Sarah J. P.
    Pearce-Kelling, Susan E.
    Mullins, Robert F.
    Graphodatsky, Alexander S.
    Ripoll, Daniel
    Felix, Jeanette S.
    Stone, Edwin M.
    Acland, Gregory M.
    Aguirre, Gustavo D.
    GENOMICS, 2006, 88 (05) : 551 - 563
  • [26] A novel ABCD1 gene mutation causes adrenomyeloneuropathy in a Chinese family
    Wang, Chao
    Liu, Hongchao
    Han, Bing
    Zhu, Hui
    Liu, Jingyao
    BRAIN AND BEHAVIOR, 2019, 9 (10):
  • [27] Identification of Novel Deletions as the Underlying Cause of Retinal Degeneration in Two Pedigrees
    Branham, Kari
    Guru, Aditya A.
    Kozak, Igor
    Biswas, Pooja
    Othman, Mohammad
    Kishaba, Kameron
    Mansoor, Hassan
    Riazuddin, Sheikh
    Heckenlively, John R.
    Riazuddin, S. Amer
    Hejtmancik, J. Fielding
    Sieving, Paul A.
    Ayyagari, Radha
    RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY, 2018, 1074 : 229 - 236
  • [28] An ENU-Induced Mutation in the Mertk Gene (Mertknmf12) Leads to a Slow Form of Retinal Degeneration
    Maddox, Dennis M.
    Hicks, Wanda L.
    Vollrath, Douglas
    LaVail, Matthew M.
    Naggert, Juergen K.
    Nishina, Patsy M.
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (07) : 4703 - 4709
  • [29] A novel missense mutation in the Connexin 26 gene associated with autosomal recessive nonsyndromic sensorineural hearing loss in a consanguineous Tunisian family
    Alemanno, Maria Stella
    Cama, Ellona
    Santarelli, Rosamaria
    Carella, Massimo
    Zelante, Leopoldo
    Toffolatti, Luisa
    Palladino, Teresa
    Melchionda, Salvatore
    Arslan, Edoardo
    INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, 2009, 73 (01) : 127 - 131
  • [30] THE CHARACTERIZATION OF RETINAL PHENOTYPE IN A FAMILY WITH C1QTNF5-RELATED LATE-ONSET RETINAL DEGENERATION
    Vincent, Ajoy
    Munier, Francis L.
    Vandenhoven, Cynthia C.
    Wright, Tom
    Westall, Carol A.
    Heon, Elise
    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES, 2012, 32 (08): : 1643 - 1651