1: Ophthalmic Genet. 2010 Jun 30; [Epub ahead of print] 

PITPNM3 is an uncommon cause of cone and cone-rod dystrophies.

Kohn L, Kohl S, Bowne SJ, Sullivan LS, Kellner U, Daiger SP, Sandgren O,
Golovleva I.

Department of Medical Biosciences, Medical and Clinical Genetics, Umea
University, Sweden.

The first mutation in PITPNM3, a human homologue of the Drosophila retinal
degeneration (rdgB not not) gene was reported in two large Swedish families with
autosomal dominant cone dystrophy. To establish the global impact that PITPNM3
has on retinal degenerations we screened 163 patients from Denmark, Germany, the
UK, and USA. Four sequence variants, two missence mutations and two intronic
changes were identified in the screen. Thus, mutations in PITPNM3 do not appear
to be a major cause of cone or cone-rod dystrophy.

PMID: 20590364  [PubMed - as supplied by publisher]

2: Ophthalmic Genet. 2010 Jun 23; [Epub ahead of print] 

Clinical Characterization and Proposed Mechanism of Juvenile Glaucoma-A Patient
with a Chromosome 4p Deletion, Wolf-Hirschhorn Syndrome.

Curtin J, Moloney G, Grigg J, Sharota Franzco D.

Ophthalmology Department, Sydney Eye Hospital, New South Wales, Australia.

The case presented is that of a 22-year-old male with Wolf-Hirschhorn syndrome
who was referred with glaucoma refractory to medical treatment. Six other
patients have been described with Wolf-Hirschhorn syndrome (WHS) and glaucoma,
most being congenital glaucoma with diagnosis in infancy. We describe the first
case of juvenile onset glaucoma in this syndrome. Our patient had narrow angles
on gonioscopy, with ultrasound biomicroscopy revealing ciliary body cysts. We
alert others to the possibility of this mechanism of secondary narrow angle
glaucoma associated with this chromosomal deletion syndrome.

PMID: 20569021  [PubMed - as supplied by publisher]

3: Ophthalmic Genet. 2010 Jun 23; [Epub ahead of print] 

Long-term 12 year follow-up of X-linked congenital retinoschisis.

Kjellstrom S, Vijayasarathy C, Ponjavic V, Sieving PA, Andreasson S.

Department of Ophthalmology, Lund University, Lund, Sweden.

Purpose: To investigate the retinal structure and function during the
progression of X-linked retinoschisis (XLRS) from childhood to adulthood.
Methods: Ten patients clinically diagnosed with XLRS were investigated at 6-15
years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12
years). The patients underwent regular ophthalmic examination as well as testing
of best corrected visual acuity (BCVA), visual field (VF) and assessment of
full-field electroretinography (ERG) during their first visit. During the
follow-up, the same clinical protocols were repeated. In addition, macular
structure and function was examined with multifocal electroretinography (mfERG)
and optical coherence tomography (OCT). The patients were 18-25 years of age
(mean age 21 years) at the follow-up examination. All exons and exon-intron
boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10
patients. Results: Best corrected VA and VF were stable during this follow-up
period. No significant progression in cone or rod function could be measured by
full-field ERG. Multifocal electroretinography and OCT demonstrated a wide
heterogeneity of macular changes in retinal structure and function at the time
of follow-up visit. Three different mutations were detected in these nine
patients, including a known nonsense mutation in exon 3, a novel insertion in
exon 5 and an intronic mutation at 5' splice site of intron 3. Conclusions:
Clinical follow-up (mean 12 years) of ten young XLRS patients (mean age of 9
years) with a typical congenital retinoschisis phenotype revealed no significant
decline in retinal function during this time period. MfERG and OCT demonstrated
a wide variety of macular changes including structure and dysfunction. The XLRS
disease was relatively stable during this period of observation and would afford
opportunity for therapy studies to judge benefit against baseline and against
the fellow eye.

PMID: 20569020  [PubMed - as supplied by publisher]

4: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

Mutation screen of beta-crystallin genes in 274 patients with age-related
macular degeneration.

Sturgill GM, Bala E, Yaniglos SS, Peachey NS, Hagstrom SA.

Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland,
Ohio, USA.

Purpose: The crystallin family of proteins comprise the main structural proteins
of the vertebrate lens and have been classified into alpha-, beta-, and gamma-
families. Several of the beta-crystallin proteins have been detected in the
retina where they are each localized to different compartments of rod and cone
photoreceptors. Functionally, beta-crystallins have been implicated in the
protection of the retina from intense light exposure. Two members of the
beta-crystallins, CRYBB1 and CRYBB2, have been identified in drusen preparations
isolated from the retina of donor eyes of patients with age-related macular
degeneration (AMD), the leading cause of blindness in the elderly population of
developed countries. We therefore investigated CRYBB1 and CRYBB2 as candidate
genes for AMD in 274 unrelated patients. Results: A mutation screen of the
entire coding region of the CRYBB1gene uncovered eight sequence variations,
including three missense changes, two intronic changes and three isocoding
changes. A mutation screen of the entire coding region of the CRYBB2 gene
uncovered three sequence variations, one isocoding change and two intronic
changes. Conclusions: Although variant alleles of the CRYBB1 and CRYBB2 genes
were found, none are considered pathogenic.

PMID: 20565250  [PubMed - as supplied by publisher]

5: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

Leber's hereditary optic neuropathy: Clinical and molecular profile of a
Brazilian sample.

Maciel-Guerra AT, Zanchetta LM, Amaral Fernandes MS, Andrade PB, do Amor Divino
Miranda PM, Sartorato EL.

Departamento de Genetica Medica, Faculdade de Ciencias Medicas, Universidade
Estadual de Campinas, Sao Paulo, Brasil.

Purpose: The aim of this study was to describe clinical features and search for
primary mitochondrial DNA (mtDNA) mutations in 13 unrelated Brazilian patients
with Leber's hereditary optic neuropathy (LHON). Methods: Analysis of the
G11778A, G3460A, and T14484C mutations was done by polymerase chain reaction and
restriction fragment length polymorphism, and mutations were confirmed by direct
sequencing. Mean age of onset was 24.5 years and all cases were bilateral.
Results: Sex ratio (12M:1F) and frequency of simultaneous involvement (9/13)
were higher than in other studies. In nine cases there was familial recurrence:
24 male and two female relatives. Ten patients had a mutation: G11778A in six,
T14484C in three and one G3460A. The frequency of patients bearing a primary
mutation was lower than that described in multicentric studies but similar to
that observed among Asians. A higher frequency of the T14484C mutation was
detected. Conclusions: The contribution of Amerindians and Africans to the
Brazilian mtDNA pool may account for differences in the type and frequency of
primary LHON mutations.

PMID: 20565249  [PubMed - as supplied by publisher]

6: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

eNOS Gene Polymorphism Association with Retinopathy in Type 1 Diabetes.

Bazzaz JT, Amoli MM, Pravica V, Chandrasecaran R, Boulton AJ, Larijani B,
Hutchinson IV.

Endocrinology and Metabolism Research Center (EMRC), Tehran University of
Medical Sciences, Tehran, Iran.

Purpose: Nitric oxide (NO) is a major mediator in vascular biology, regulating
blood pressure and regional blood flow. NO and the enzymes required for its
production may contribute to the aetiology of vascular pathologies. In diabetes,
over-production of NO might play a role in the development of diabetic
nephropathy, while reduced NO production may be related to the development of
diabetic retinopathy and neuropathy, where VEGF (vascular endothelial growth
factor) levels are increased in a counter regulatory manner. Among the three
nitric oxide synthase (NOS) enzymes most attention has focussed on endothelial
NOS (eNOS) because of its relevance to angiopathies. Methods: In this study the
influence of a single nucleotide polymorphism at position -786 in the eNOS gene,
where there is a C/T base substitution, on development of type 1 diabetes
mellitus (T1DM) and its microvascular complications was studied in 249 British
Caucasian type 1 diabetics using a case-control association design. Genotyping
was carried out using PCR-RFLP technique. Results: There was a significant
association between the polymorphism -786*C/T and both T1DM and diabetic
retinopathy. The distribution of eNOS gene polymorphism genotype frequencies
showed a significant difference observed between diabetic patients and healthy
controls [CC+CT vs. TT p = 0.05, OR = 1.5 95%CI(0.9-2.5)]. The genotype
frequencies for eNOS gene polymorphism was also significantly different between
diabetic retinopaths and healthy controls [CC+CT vs. TT p = 0.0000 OR = 3.4
95%CI(1.9-6.1) No significant differences for eNOS allele and genotype
frequencies were found in other groups compared to the controls. Conclusion:
Therefore, eNOS gene variation may be a factor in the genetic propensity to T1DM
and diabetic retinopathy that may have a prognostic value or may suggest
interventional approaches to regulate eNOS in patients with diabetes.

PMID: 20565248  [PubMed - as supplied by publisher]

7: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

The relationship between ACE gene insertion/deletion polymorphism and diabetic
retinopathy in Iranian patients with type 2 diabetes.

Nikzamir A, Rashidi A, Esteghamati A, Nakhjavani M, Golmohammadi T, Khalilzadeh
O.

Department of Biochemistry, Ahwaz Jondi Shapour University of Medical Sciences,
Ahwaz, Iran.

Background: The role of genetic factors in diabetic retinopathy (DR) is unclear.
We investigated the relationship between DR and an insertion/deletion
polymorphism in the angiotensin-converting enzyme (ACE) gene in Iranian patients
with type 2 diabetes without overt nephropathy. Methods: A total of 178
consecutive type 2 diabetic patients with DR (Group A) and 206 type 2 diabetic
patients without DR (Group B) were studied. The following variables were
determined: age, sex, body mass index, diabetes duration, medications used,
history of coronary artery disease and its complications, blood pressure
(systolic and diastolic), fasting plasma glucose, hemoglobin A1c, total
cholesterol, low- and high-density lipoproteins, triglycerides, plasma
creatinine, and 24-h urine albumin excretion. Results: The groups were
statistically similar in all variables except diabetes duration (P = 0.037), ACE
activity (P < 0.001), and ACE genotype (P = 0.008). The DD genotype was
significantly more common in Group A (32.6% versus 19.2% in Group B; P = 0.009).
In multivariate regression analysis, the ID genotype (compared to the II
genotype) was an independent predictor of DR (OR = 1.831, 95% CI = 1.074-3.124;
P = 0.026). Conclusions: The D allele of the ACE gene is independently
associated with DR in Iranian type 2 diabetic patients.

PMID: 20565247  [PubMed - as supplied by publisher]

8: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

Optic disk and white matter abnormalities in a patient with a de novo 18p
partial monosomy.

Abu-Amero KK, Hellani A, Salih MA, Alorainy IA, Zidan G, Kern KC, Sicotte NL,
Bosley TM.

Department of Ophthalmology, College of Medicine, King Saud University, Riyadh,
Saudi Arabia.

Purpose: Neuro-ophthalmologic and neuroimaging features of partial chromosome
18p deletion syndromes have not yet been fully described. Methods: Careful
neuro-ophthalmologic and neuroimaging evaluation of a young woman with a partial
18p deletion, including 3 Tesla MRI and diffusion tensor imaging, cytogenetic
analysis on GTG-banded chromosomes, and 244K array CGH analysis. Results: This
17-year-old girl had modest mental retardation, facial dysmorphism, other
characteristics typical of 18p deletion syndrome, and anomalous optic disks. MRI
showed enlarged third and lateral ventricles, a thin corpus callosum and patchy
white matter signal hyperintensities without enhancement, while diffusion tensor
imaging (DTI) revealed significant abnormalities of the corpus callosum with
relative sparing of the corticospinal tracts. She had a de novo 14.6 Mb deletion
on chromosome 18p [del(18)(p11.2>pter)], a region including 143 genes, only 10
of which were likely candidates for phenotypic expression. Conclusions: This
young woman had clinical features similar to those described previously with the
18p deletion syndrome, including moderate mental retardation and dysmorphism
without focal neurologic signs. She was myopic, like other 18p deletion
patients, supporting the concept that 18p contains a candidate locus for myopia.
She also had anomalous optic disks, a feature that may be more common in this
syndrome than previously recognized. MRI revealed enlarged ventricles and white
matter abnormalities that may be explained in part by haploinsufficiency of
ADCYAP1 and LPIN2 in the deleted region of chromosome 18.

PMID: 20565246  [PubMed - as supplied by publisher]

9: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

Familial case of Blau syndrome associated with a CARD15/NOD2 mutation.

Villanueva-Mendoza C, Arellanes-Garcia L, Cubas-Lorenzo V, Jimenez-Martinez MC,
Flores-Suarez LF, Zenteno JC.

Asociacion para Evitar la Ceguera en Mexico, Genetics, Mexico City, Mexico.

Purpose: Blau syndrome is a rare autosomal dominant disorder characterized by
early onset granulomatous arthritis, uveitis, skin rash and camptodactyly. We
report a familial case of Blau syndrome associated with a CARD15/NOD2 mutation.
Methods: PCR amplification and automated DNA sequencing of the complete
CARD15/NOD2 coding sequence was performed. Results: Molecular analysis in
affected subjects disclosed a heterozygous c.1147G>C point mutation in
CARD15/NOD2 exon 4, that predicts a p.E383K change at the protein level.
Conclusions: Blau syndrome should be considered in the differential diagnosis of
childhood uveitis and the genetic analysis of the CARD15/NOD2 gene is helpful in
the diagnosis.

PMID: 20565245  [PubMed - as supplied by publisher]

10: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

CDKN1C (p57KIP2) mRNA expression in human retinoblastomas.

Madhavan J, Mallikarjuna K, Vikas K, George R, Bremner R, Kumaramanickavel G.

SN ONGC Department of Genetics & Molecular Biology, Vision Research Foundation,
Sankara Nethralaya, Tamil Nadu, India.

Purpose: Quantify cyclin dependent kinase inhibitor 1C (CDKN1C or p57KIP2) mRNA
levels in human retinoblastoma tumors (RB) and associate with disease phenotype.
Methods: CDKN1C mRNA expression was quantified in 55 RB, 3 retinoblastoma cell
lines, and 12 control retinas by real time PCR. Localization of CDKN1C protein
was confirmed by immunohistochemistry. Tumor CDKN1C expression levels were
correlated with phenotype. Results: Fifty-three of 55 tumors showed
significantly elevated levels of CDKN1C mRNA relative to age-matched or adult
retina controls. No significant difference was seen relative to fetal retinal
controls or retinoblastoma cell lines. Immunohistochemistry revealed
heterogeneous staining of CDKN1C protein in tumor cells, which was mainly
nuclear although some protein appeared to be cytoplasmic. No correlation was
observed between the CDKN1C mRNA expression levels and tumor phenotype.
Conclusion: High levels of CDKN1C expression are common in RB. It remains to be
determined if elevated expression is a protective response to transformation,
provides a selective advantage to tumor cells, or simply reflects the presence
of dividing cells.

PMID: 20565244  [PubMed - as supplied by publisher]

11: Ophthalmic Genet. 2010 Jun 21; [Epub ahead of print] 

RB pocket domain B mutation frequency in Malaysia.

Ishak SR, Hanafi H, Alagaratnam JV, Zilfalil BA, Tajudin LS.

Department of Ophthalmology, School of Medical Sciences, Health Campus,
Universiti Sains Malaysia, Kelantan, Malaysia.

PMID: 20565234  [PubMed - as supplied by publisher]