Ophthalmic Genetics (OPHTHALMIC GENET)

Publications in this journal

• Article: Balanced translocation (t 2q; 10p) and ocular anomalies. A possible HOX gene defect.

  P Nucci, M P Manitto, A Faiella, E Boncinelli, R Brancato
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  ABSTRACT: The authors report a child with a phenotype typical of a first branchial arch defect. The patient has a balanced translocation involving chromosome 2. They propose a defect that has occurred during the translocation in a gene mapped to chromosome 2 and belonging to the HOXD family. HOX gene defects can perturb the expression of other genes important for head development.
  Ophthalmic Genetics 07/2009; 15(3-4):129-31.
• Article: Reassessment of the pathologic significance of the 9438 mitochondrial DNA mutation associated with LHON.

  Khaled K Abu-Amero, Thomas M Bosley
  Ophthalmic Genetics 01/2008; 28(4):229-30.
• Article: LOC387715/HTRA1 and complement factor H variants in patients with age-related macular degeneration seen at the mayo clinic.

  Jose S Pulido, Lisa M Peterson, Lejla Mutapcic, Sandra Bryant, W Edward Highsmith
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  ABSTRACT: To confirm association of the complement factor H allelic variant (CFH Y402H) and the LOC387715/HTRA1 (LOC387715 A69S) risk alleles with age-related macular degeneration (AMD). Study of 89 Caucasian patients with neovascular (exudative) AMD and 232 Caucasian controls. The Y402H variant of CFH gene and A69S variant of LOC387715/HTRA1 gene locus were examined. For CFH, the odds ratio for the homozygous variant was 4.97 (CI 2.52 to 9.79). For LOC387715/HTRA1 the odds ratio for the homozygous risk variant was 7.75 (CI 3.46 to 17.35). The odds ratio for heterozygous carriers was 3.35 (CI 1.91 to 5.90).
  Ophthalmic Genetics 01/2008; 28(4):203-7.
• Article: Two novel deletions (array CGH findings) in pigment dispersion syndrome.

  Ruth Mikelsaar, Harras Molder, Oliver Bartsch, Margus Punab
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  ABSTRACT: We report the first male with pigment dispersion syndrome and a balanced translocation t(10;15)(p11.1;q11.1). Cytogenetic analyses using Giemsa banding and FISH methods, and array CGH were performed. Array CGH analyses did not show altered DNA sequences in the breakpoints of the translocation, but revealed two novel deletions in 2q22.1 and 18q22.1. We suppose that the coexistence of t(10;15) and pigment dispersion syndrome in our patient is a coincidence. The deletion in 2q22.1, where the gene LRP1B has been located, may play a major role in the dysembryogenesis of the eye and cause the disorder.
  Ophthalmic Genetics 01/2008; 28(4):216-9.
• Article: A review of the molecular genetics of congenital Idiopathic Nystagmus (CIN).

  James Self, Andrew Lotery
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  ABSTRACT: Congenital Idiopathic Nystagmus (CIN) is genetically heterogeneous. Autosomal dominant, autosomal recessive and X-linked patterns of inheritance have been reported. Linkage analysis has suggested the existence of at least three distinct loci for both autosomal dominant and X-linked forms, although only one disease gene has been identified (FRMD7, Xq26.2). The pathophysiological mechanisms underlying nystagmus are poorly understood but it is anticipated that characterization of the FRMD7 gene and identification of novel nystagmus genes will provide insights into this condition and the functioning and development of the visual pathways in general.
  Ophthalmic Genetics 01/2008; 28(4):187-91.
• Article: Chorioretinopathy and microcephaly with normal development.

  Hoda Ahmadi, Yasmin S Bradfield
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  ABSTRACT: Purpose: To report a pediatric patient with bilateral chorioretinopathy and microcephaly who from birth to 2 years of age is reaching appropriate developmental milestones. Design: Retrospective case report with clinical findings and literature review. Main Outcome Measures: Clinical findings and visual acuity estimated by sweep visual evoked potentials (VEP), electroretinogram (ERG) and fundoscopic exam. Results: A microcephalic child with normal motor and cognitive development had improving sweep VEP despite atypical fundoscopic findings of bilateral chorioretinopathy, attenuated retinal vessels, and anomalous optic nerves. The etiology for these collective findings despite extensive workup, including prenatal TORCH titers and neuro-imaging, has remained unidentified. Conclusions: Most published cases of microcephaly with chorioretinopathy have described patients with mild to severe mental retardation. Patients with chorioretinopathy and microcephaly may, however, reach all developmental milestones with improvement in visual development as was seen in this case. The long-term cognitive and visual prognosis may be better than previously reported.
  Ophthalmic Genetics 01/2008; 28(4):210-5.
• Article: Severe form of familial exudative vitreoretinopathy caused by homozygous R417Q mutation in frizzled-4 gene.

  Hiroyuki Kondo, Minghui Qin, Tomoko Tahira, Eiichi Uchio, Kenshi Hayashi
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  ABSTRACT: To report the clinical features of a patient with familial exudative vitreoretinopathy (FEVR) associated with homozygous R417Q mutation in the frizzled-4 gene (FZD4). Clinical examination and mutation analysis by direct sequencing. A five-month-old girl was found to have leukocoria associated with retrolental fibroplasia in the right eye and a severe falciform retinal fold in the left eye. Mutational analysis revealed a homozygous R417Q mutation in the FZD4 gene. Her parents who carried the same mutation heterozygously exhibited milder ocular phenotype. Homozygous state for the FZD4 gene is possibly involved in the severity of the FEVR phenotype.
  Ophthalmic Genetics 01/2008; 28(4):220-3.
• Article: A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features.

  David Rivera de la Parra, Juan Carlos Zenteno
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  ABSTRACT: Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder that includes a clinical spectrum of craniofacial, neurologic, limb, and ocular malformations. The disease is caused by heterozygous mutations in the 6q22-q23 located GJA1 gene, that encodes connexin 43 (Cx43). In this paper we describe a novel Cx43 mutation (G2V) found in a Mexican eight-year-old boy. This de novo mutation predicts a missense substitution at the second amino acid of Cx43, in the first intracellular domain, and is the most amino-terminal located mutation reported so far. Umbilical hernia and congenital optociliary veins, two uncommon ODDD-associated features, were recognized in our patient. The phenotype of three previously described patients with Cx43 first intracellular domain mutation is discussed and compared with that observed in our patient. This case expands the phenotypic and genotypic spectrum of ODDD.
  Ophthalmic Genetics 01/2008; 28(4):198-202.
• Article: Lens coloboma associated with a ciliary body cyst.

  Arif O Khan, Abdullah Al-Assiri
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  ABSTRACT: Isolated congenital lens coloboma is a sectoral indentation of the crystalline lens due to zonular weakness or absence. The purpose of this report is to describe the association of lens coloboma with an adjacent cyst in the ciliary body and to suggest that ciliary body cysts may be an under-recognized cause of congenital lens coloboma.
  Ophthalmic Genetics 01/2008; 28(4):208-9.
• Article: Pseudo-vitelliform macular detachment and cuticular drusen: exclusion of 6 candidate genes.

  Irene A Barbazetto, Nicolas A Yannuzzi, Christina M Klais, Joanna E Merriam, Jana Zernant, Enrico Peiretti, Lawrence A Yannuzzi, Rando Allikmets
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  ABSTRACT: The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes. Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing. All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population. Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype.
  Ophthalmic Genetics 01/2008; 28(4):192-7.
• Article: Genetic screening of leber congenital amaurosis in a large consanguineous Iranian family.

  Tayebeh Rezaie, Mohammad-Hassan Karimi-Nejad, Mohammad-Reza Meshkat, Saeed Sohbati, Roxana Karimi-Nejad, Hossein Najmabadi, Mansoor Sarfarazi
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  ABSTRACT: The molecular defect of one large consanguineous Iranian kindred with Leber Congenital Amaurosis (LCA) is presented. The phenotype mapped to 17p13.1 (LCA1) and excluded from five other LCA loci. Sequence analysis of the GUCY2D gene identified a novel homozygous missense mutation (I816S) that segregated with the inherited disease-haplotype in six affected, eight parents, and two normal gene carriers. This mutation was absent in three other normal family members and 92 normal control subjects. In silico analysis predicted that alteration of the highly conserved isoleucine residue at position 816 to serine is deleterious by affecting secondary structure of the GUCY2D protein.
  Ophthalmic Genetics 01/2008; 28(4):224-8.
• Article: Choroideremia is caused by a defective phagocytosis by the RPE of photoreceptor disc membranes, not by an intrinsic photoreceptor defect.

  Robert K Koenekoop
  Ophthalmic Genetics 10/2007; 28(3):185-6.
• Article: Qualitative research methodology in the exploration of patients' perceptions of participating in a genetic research program.

  Frieda Basson, Merle Joyce Futter, Jacquie Greenberg
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  ABSTRACT: The success of genetic research studies depend on patients' willingness to participate. It is thus important to explore the attitudes of individuals that participate in such studies. This study used qualitative methods to explore how individuals with inherited retinal degenerative disorders (RDD) perceived participating in genetic research and subsequently receiving mutation results. Individual interviews were conducted with all the individuals in the Cape Town Metropolitan area who had received mutation results after participating in a genetic research program (4 individuals). Although experiences differed significantly, the study revealed that the participants had positive attitudes towards participating in the RDD research program. This study illustrates the importance of using qualitative methods in ophthalmic populations to explore important issues.
  Ophthalmic Genetics 10/2007; 28(3):143-9.
• Article: Novel mutations in the KCNV2 gene in patients with cone dystrophy and a supernormal rod electroretinogram.

  Sureka Thiagalingam, Terri L McGee, Richard G Weleber, Michael A Sandberg, Karmen M Trzupek, Eliot L Berson, Thaddeus P Dryja
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  ABSTRACT: To identify mutations in KCNV2 in patients with a form of cone dystrophy characterized by a supernormal rod electroretinogram (ERG). The 2 exons and flanking intron DNA of KCNV2 from 8 unrelated patients were PCR amplified and sequenced. We found 1 frameshift, 2 nonsense, 1 non-stop, and 6 missense mutations. Every patient had one or two mutations identified. Of the missense mutations, 4 affected residues were in the amino terminal region of the protein, and two in the pore region. KCNV2 mutations account for most if not all cases of cone dystrophy with a supernormal rod ERG.
  Ophthalmic Genetics 10/2007; 28(3):135-42.
• Article: Optic nerve dysfunction in a child following low-dose maternal warfarin exposure.

  Arif O Khan
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  ABSTRACT: Because the embryopathy associated with maternal warfarin use seems dose-dependent, some physicians advocate low-dose warfarin for pregnant women requiring anticoagulation. The current case, however, highlights that optic nerve dysfunction (as well as other signs of warfarin embryopathy) can occur after low-dose maternal warfarin exposure.
  Ophthalmic Genetics 10/2007; 28(3):183-4.
• Article: The retinal ciliopathies.

  N A Adams, Ahmed Awadein, Hassanain S Toma
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  ABSTRACT: While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present.
  Ophthalmic Genetics 10/2007; 28(3):113-25.
• Article: Retinal dysfunction in carriers of bardet-biedl syndrome.

  Linda S Kim, Gerald A Fishman, William H Seiple, Janet P Szlyk, Edwin M Stone
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  ABSTRACT: To determine whether retinal dysfunction in obligate carriers of the Bardet-Biedl syndrome (BBS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). Six obligate carriers of the BBS were examined for the study. Examination of each carrier included an ocular examination and mfERG testing of one eye. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally sighted, age-similar control subjects. Mapping of 103 local electroretinographic response amplitudes within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes in three of six carriers. Implicit time measurements in the 6 carriers were all normal except for those locations associated with abnormal amplitude reductions in 3 of the carriers. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Multifocal ERG testing can demonstrate areas of retinal dysfunction in carriers of the BBS. This test may therefore be useful for identifying some heterozygous carriers of this disease.
  Ophthalmic Genetics 10/2007; 28(3):163-8.
• Article: Lens opacities in Bloom syndrome: case report and review of the literature.

  Kivanc Cefle, Sukru Ozturk, Nilufer Gozum, Nilgun Duman, Ferhan Mantar, Kerim Guler, Sukru Palanduz
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  ABSTRACT: Bloom syndrome is an autosomal recessive disorder characterized by proportionate short stature, photosensitivity, immunodeficiency, hypogonadism and a tendency to develop various malignancies. The greatly increased frequency of sister chromatid exchanges (reciprocal exchange of homologous segments between the two sister chromatids of a chromosome) is regarded as pathognomonic for BS. We describe an 18-year old girl who presented with short stature. She was diagnosed with BS based on an extremely increased frequency of sister chromatid exchanges. Ophthalmological examination revealed mild lens opacities bilaterally, which, to our knowledge, has not been previously reported to be associated with BS.
  Ophthalmic Genetics 10/2007; 28(3):175-8.