Showing papers in "Ophthalmic Genetics in 2005"

HEMICENTIN-1 (FIBULIN-6) and the 1q31 AMD Locus in the Context of Complex Disease: Review and Perspective

Abstract: Age-related macular degeneration (AMD) is the most common blinding disorder in the Western world. Similar to other common diseases in which age is a risk factor (e.g., type II diabetes or Alzheimer's disease), AMD is thought to have a complex etiology. Previously, a Gln5345Arg mutation in HEMICENTIN-1 was found to segregate with AMD in a large family. However, the population frequency of this allele is inconsistent with the large proportion of families shown by linkage studies to map near this gene at 1q31. This review summarizes current knowledge regarding the role of HEMICENTIN-1 in AMD, the results of association studies for the Gln5345Arg mutation, and the linkage evidence for an AMD locus on 1q31. The data can be reconciled through proposing both additional variants in HEMICENTIN-1 and a second genetic risk factor for AMD in the region.

RPGRIP1 is mutated in Leber congenital amaurosis: a mini-review.

Abstract: RPGRIP1 encodes the retinitis pigmentosa GTPase interacting protein 1 and interacts with RPGR, the latter represents the major X-linked RP (XRRP) gene, as it accounts for 70-80% of the XRRP patients and up to 13% of all RP patients. RPGRIP1 contains a C-terminal RPGR interacting domain (RID) and a coiled-coil (CC) domain, which is homologous to proteins involved in vesicular trafficking. The interactions between the two proteins is between the RCC1-homologous domain of RPGR (RHD) and the RPGR-interacting domain of RPGRIP1 (RID). Both proteins co-localize to the photoreceptor connecting cilium and RPGRIP1 appears to be a structural component of the ciliary axoneme of the connecting cilium (which connects the inner to the outer segment of the photoreceptors) of both rods and cones and functions to anchor RPGR within the cilium.RPGRIP1 loci encode several different isoforms, which have distinct cellular, sub cellular and biochemical properties. RPGRIP1 is uniquely expressed in amacrine cells of the inner retina. Knockout mice studies have shown that RPGRIP1 is required for disc morphogenesis of the outer segments in the mouse, perhaps by regulating cytoskeleton dynamics. Thus far RPGRIP1 appears to be only mutated in LCA and is associated with 6% of LCA in two series. The purpose of this review is to highlight recent advances in our understanding of RPGRIP1 function in normal and diseased retinas.

Juvenile X-linked retinoschisis with normal scotopic b-wave in the electroretinogram at an early stage of the disease.

Abstract: Purpose: To report four cases of genetically verified juvenile X-linked retinoschisis (XLRS) with normal scotopic b-waves in full-field ERG, including one patient with a novel mutation (W50X) in the RS1gene. Methods: Four XLRS patients from different families were examined with regard to visual acuity, kinetic perimetry, fundus photography, full-field ERG, and OCT. Two of these patients were also examined with multifocal-ERG (mfERG). Mutations in the RS1gene were identified by sequence analysis. Results: The full-field ERG presented normal b-wave amplitudes on scotopic white-light stimulation. OCT and mfERG presented macular schisis and macular dysfunction. Genetic analysis revealed a deletion of exon 1 and the promotor region in one patient and mutations giving rise to the amino acid substitutions R209C and W96R in two others. The fourth patient carried a novel mutation in exon 3 of the RS1 gene (nt 149 G→A), causing the introduction of a stop codon after amino acid 49 in the RS protein. Conclusion: Four...

Penetrance and phenotype of the Thr377Met Myocilin mutation in a large Finnish family with juvenile- and adult-onset primary open-angle glaucoma

Abstract: Purpose: To study the role of myocilin (MYOC) as a susceptibility gene for juvenile- and adult-onset open-angle glaucoma (JOAG and POAG, respectively). Methods: In a six-generation Finnish family with JOAG and POAG, we performed thorough ophthalmologic characterization (including assessment of the visual fields by Octopus perimetry, nerve-fiber layer thickness by photography, and disc size by Heidelberg tomography) of 51 individuals. The coding region of MYOC was screened for mutations by PCR amplification and direct sequencing. Results:We detected a C > T transition at codon 377 resulting in a substitution of a threonine residue for methionine (Thr377Met) in the olfactomedin-like domain of myocilin, segregating in the family. Of the 20 individuals heterozygous for the mutation, nine (45%) were glaucomatous and two (10%) had ocular hypertension (OHT). The mean age at diagnosis of glaucoma in these individuals was 34.3 years (range: 14-66 years). Moreover, three of these individuals suffered retinal vein o...

Posterior Polar Cataract: Genetic Analysis of a Large Family

Abstract: Congenital cataracts are clinically and genetically heterogeneous. Loci for autosomal dominant posterior polar cataracts have been mapped to chromosomes 1p36, 11q22-q22.3, 16q22, and 20p12-q12. We investigated a large four-generation family with 20 individuals affected with congenital posterior polar cataracts. After exclusion of known loci for posterior polar cataracts, a genome-wide screen was conducted. In this family, we mapped dominant congenital posterior polar cataracts to chromosome 10q24. On haplotype analysis, we identified an 11-cM interval between loci D10S1680 and D10S467, which included the PITX3 gene. On sequencing the coding region of PITX3, we found a 17-base-pair duplication in exon 4. Although the same genotype was described in a family with ASMD and cataracts, the common phenotype of this mutation is probably posterior polar cataract; a modifier gene is presumed to cause anterior segment abnormalities in the previously described patients. The same mutation was recently identified in four families with congenital cataracts. This study provides further evidence of genetic heterogeneity of autosomal dominant posterior polar cataract.

Multiple congenital malformations including severe eye anomalies and abnormal cerebellar development with Dandy-Walker malformation in a girl with partial trisomy 3q.

Abstract: Purpose: Ocular anomalies have been associated with numerous chromosomal abnormalities. This report describes partial trisomy 3q in a two-month-old girl with dysmorphic features of the Dup3q phenotype and severe eye and cerebellar malformations. Methods: Clinical examination and chromosomal analysis were conducted. Results: The karyotype of the propositus was 46,XX, ins(3)(pter → p25::q27 → q21::p25 → qter). She had an abnormal head shape, low-set malformed ears, coarse facies, short webbed neck, abnormal foot position, polycystic kidney, and spina bifida. There was also bilateral microphthalmia that was more severe on the right side, microcornea, and corneal opacity. She had posterior fossa abnormalities, including cerebellar vermis hypoplasia suggestive of a Dandy-Walker (DW) malformation. Conclusions: This girl with an intrachromosomal duplication of distal 3q and typical phenotype belongs to the severe end of the spectrum for such cases. The ocular manifestations of the 3q duplication syndrome provide...

Hereditary High Hypermetropia in the Faroe Islands

Abstract: Purpose: To characterize the phenotype of two families with high hypermetropia from the Faroe Islands. Methods: Ophthalmologic evaluation including ultrasound oculometry and anthropometric measurements. Results: Of the 40 examined family members, 15 individuals (8 males, 7 females; ages: 6-77 years; mean: 36.5 years) had small deep-set eyes with high hypermetropia (median: + 16.5 D; range: + 7.75 to + 22), short axial eye length (< 21 mm), and a thickened eye wall. The median corrected visual acuity was 0.4 (0.2-0.9). Ocular complications included angle-closure glaucoma in six eyes, uveal effusion in three eyes, cataract in two eyes, and esotropia with amblyopia in three eyes. An emergency case of uveal effusion and retinal detachment after Yag iridotomy eventually responded to systemic corticosteroids and scleral resection surgery with a slow visual recovery. No associated ocular or systemic malformations were found in the series. In addition to the two examined families, six smaller Faroese families wit...

Mitochondrial T9957C mutation in association with NAION and seizures but not MELAS.

Abstract: Purpose: To assess the functional significance of the mitochondrial nt-9957 mutation in a man with non-arteritic ischemic optic neuropathy (NAION). This nt-9957 mutation has been previously reported in association with mitochondrial encephalopathy, lactic acidosis, and stroke-like events (MELAS). Methods: The patient was examined clinically and with magnetic resonance imaging and spectroscopy. The entire coding region of the mitochondrial genome was sequenced, and mitochondrial function was assessed by flow cytometry after staining with fluorescent dihydroethidium. Results: This 76-year-old man had optic nerve disease bilaterally and seizures, but no clinical or radiological evidence of MELAS. He had no mitochondrial DNA mutation other than the 9957. Functional testing revealed a severe defect in mitochondrial complex III activity. Conclusions: This patient had a mitochondrial functional deficit consistent with his 9957 mutation. It seems quite likely that this mutation may be responsible for optic nerve ...

The mouse's eye and Mfrp: not quite human.

Abstract: The laboratory mouse, Mus musculus, is a key model experimental system for approaching the genetics, development, and physiology of the human eye. So useful has it been for investigating the basis of human ocular disorders that we often overlook the substantial differences between the two species. There are, however, major anatomical differences. The mouse lens is closer to spherical in shape than the human lens and it occupies most of the vitreal cavity. This arrangement in rodents is reminiscent of the fish eye and should provide uniform optical focus over a wider field of view, which would be of advantage to a small prey animal.1 The mouse retina is adapted to a nocturnal and crepuscular lifestyle and has fewer numbers and types of cone photoreceptors. At the back of the eye, it lacks a foveal pit and shows no evidence of a macular clustering of cones. It also has unusual photoreceptor adaptations not found in humans. In the mouse, the middle wavelength (red-green) cone type is segregated in the superior retina, while the blue cone type is restricted to the inferior half of the retina.2 Less obvious are the underlying genetic differences, which have often been unexpected and remain poorly understood. One such difference is illustrated in the paper by Pauer and coworkers, appearing in this issue.3 Their work builds on the discovery of MFRP, which encodes a 579-amino acid protein with a single transmembrane domain near the N-terminus and five globular extracellular domains homologous to cubilin, the LDL receptor, and the Wnt-binding domain of Frizzled.4 Three years ago, the mouse mutant rd6 was mapped and identified as a splice-site mutation in the orthologous Mfrp gene, which was found to be expressed primarily in the mouse eye, specifically the retinal pigment epithelium (RPE) and ciliary body.5 The rd6 mouse undergoes a slow degeneration of photoreceptors, and during this process the fundus develops a distinctive array of depigmented spots (Fig. 1A) that bear very striking resemblance to the human retinal degenerative disorders Stargardt disease (Fig. 1B) and fundus albipuctatus.6 Pauer and colleagues screened patients with Stargardt disease and a variety of other retinal degenerations for the presence of mutations and

Histopathologic-Genotypic Correlations in Retinitis Pigmentosa and Allied Diseases

Abstract: This paper reviews the published histopathologic findings of patients with retinitis pigmentosa (RP) or an allied disease in whom the responsible gene defect was identified, including 10 cases with dominant RP (cases with mutations in RHO, PRPC8, and RP1), three with dominant spinocerebellar ataxia (SCA7), three X-linked RP carrier females (RPGR), two with congenital retinal blindness (AIPL1 and RPE65), two with mitochondrial encephalomyopathy overlap syndrome (MTTL1), and one case each with dominant cone degeneration (GCAP1), X-linked cone degeneration (RCP), enhanced S-cone syndrome (NR2E3), and dominant late-onset retinal degeneration (CTRP5). No histopathologic descriptions were found of the vast majority of genetically defined forms of retinal degeneration.

Novel mutations in MYO7A and USH2A in Usher syndrome.

Abstract: Purpose: Usher syndrome is an autosomal recessive disease associating retinitis pigmentosa and neurosensory deafness. Three clinical types (USH1, USH2, USH3) and 11 mutated genes or loci have been described. Mutations in MYO7A and USH2A are responsible for about 40% and 60% of Usher syndromes type 1 and 2, respectively. These genes were screened in a series of patients suffering from Usher syndrome. Methods: We performed SSCP screening of MYO7A in 12 unrelated patients suffering from Usher syndrome type 1 (USH1) and USH2A in 28 unrelated patients affected by Usher syndrome type 2 (USH2). Results/conclusions: Six mutations in MYO7A were found in five patients, including two novel mutations c.397C>G (His133Asp) and 1244-2A>G (Glu459Stop), accounting for 42% of our USH1 patients. Twelve mutations in USH2A were found in 11 patients, including four new mutations c.850delGA, c.1841-2A >G, c.3129insT, and c.3920C>G (Ser1307Stop), accounting for 39% of our USH2 patients.

Meesmann corneal dystrophy (MECD): report of 2 families and a novel mutation in the cornea specific keratin 12 (KRT12) gene.

Abstract: Purpose: Meesmann corneal dystrophy (MECD) is an autosomal dominant disorder affecting the corneal epithelium. It is caused by heterozygous mutations in KRT3 or KRT12 gene. Actually, 14 mutations have been reported, 1 in KRT3 and 13 in KRT12. These genes were screened in several patients suffering from MECD. Methods: Patients from 2 families were screened for mutation in KRT3 and KRT12. Exons were PCR-amplified and directly sequenced. The new mutation was checked by DHPLC in 51 control individuals of Swiss origin. Results/Conclusions: In one family, the M129T heterozygous mutation was observed in KRT12. In the second family, we identified a novel I426S heterozygous mutation in exon 6 of KRT12.

Chromosomal Abnormalities and Glaucoma: A Case of Congenital Glaucoma with Trisomy 8q22-Qter/ Monosomy 9p23-Pter

Abstract: Purpose: To present a case of congenital glaucoma with an unbalanced translocation trisomy 8q22-qter/monosomy 9p23-pter, resulting in trisomy of the GLC1D locus. To perform a literature review of chromosomal abnormalities associated with glaucoma. Method: A case report of a family with balanced translocation without glaucoma and unbalanced translocation with congenital glaucoma. PubMed and OMIM databases were searched for reports of chromosomal abnormalities and glaucoma. Results: Other case reports of congenital glaucoma with chromosomal abnormalities in this region were identified. A review of cytogenetics in southeastern Australia found nine cases involving the loss of 9p23 and 10 cases involving mosaicism for trisomy 8, but none had congenital glaucoma. A review of the literature identified reports of glaucoma and chromosomal abnormalities in regions with glaucoma loci mapped by conventional linkage analysis. These include the loci GLC1B, GLC1C, GLC1D, GLC1F, GPDS1, and RIEG2. Conclusion: The study of...

A Discordant Sib-Pair Linkage Analysis of Age-Related Macular Degeneration

Abstract: Background:Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among older adults in the United States and throughout the developed world. Etiological research implicates both genetic and environmental components. Our prior genome scan in 511 affected sib-pairs and other relative pairs identified significant or suggestive linkage signals on chromosomes 1, 2, 3, 6, 8, 10, 12, 16, and 22. Purpose:To search for genetic loci for AMD using the extremely discordant sib-pair (EDSP) method of linkage analysis, which until now has never been applied to the study of AMD. Methods: The EDSP method is a more powerful approach than standard methods which rely on relative pairs selected at random or pairs concordant for the phenotype. The EDSP approach has also been characterized as the only design that is uniformly powerful in nearly all genetic situations. Thus, substantial reductions in sample size can be achieved. Study population:The study sample for analysis included 110 ...

Analysis of rare variants and common haplotypes in the optineurin gene in Swedish glaucoma cases.

Abstract: Objective: Glaucoma, a leading cause of blindness in the world, is characterized by neuropathy of the retinal ganglion cells and the optic nerve. Recently, sequence alterations in the optineuringene were shown to be associated with the disease in families with primarily normal tension glaucoma. Methods: In the present study, 200 patients with primary open-angle glaucoma, 200 patients with exfoliative glaucoma, and 200 matched controls were tested for alterations in the coding sequences using denaturing high-performance liquid chromatography and sequencing. In addition, single nucleotide polymorphisms distributed throughout the gene were typed and haplotypes were constructed. Results: No disease-causing alterations were found in either of the patient cohorts. The risk-associated allele M98K was found in equal amounts in both patients and controls. Analysis of haplotype frequencies and distribution revealed high haplotype diversity but no differences between patients and controls. Conclusion: These experime...

Clinical Phenotype in a Swedish Family with a Mutation in the IMPDH1 Gene

Abstract: Purpose: Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) have recently been discovered to cause a form of autosomal dominant retinitis pigmentosa (adRP). Such mutations are estimated to account for approximately 2–5% of the adRP cases among Americans of European origin and Europeans. Aiming towards an understanding of the molecular background of retinitis pigmentosa, this paper describes the phenotype of a Swedish family with a mutation in IMPDH1. Methods: Venous blood samples were obtained from 12 family members and screened for mutations in IMPDH1. Six individuals with the mutation were examined clinically and with full-field electroretinography (ERG), dark adaptometry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). Also reviewed were the clinical findings and ERGs obtained 14 years earlier. Results: The proband and eight other relatives from three generations were found to harbor the Asp226Asn mutation in IMPDH1. These individuals, from three genera...

X-Linked Infantile Periodic Alternating Nystagmus

Abstract: Objective: To describe the clinical and electrophysiological characterization of four family members from three generations who have X-linked infantile periodic alternating nystagmus (XIPAN). Methods: Complete clinical ophthalmological evaluation, pedigree analysis, electroretinograms (ERG), eye movement recordings (EMR), color vision, and fundus photography were performed on all subjects. Results: Three males in two generations and one female were examined. Clinical examinations showed a jerk/pendular nystagmus with a latent component, strabismus, and a significant refractive error in the three affected males, while the female had only myopic astigmatism. ERG, color contrast, and fundus examinations were normal in all four family members. All four family members showed EMR abnormalities with infantile jerk/dual jerk and pendular nystagmus waveforms. The female had nystagmus present on EMR only and all patients showed (a)periodicity to their nystagmus. Conclusions: In this family with no other congenital ...

Rieger's anomaly and other ocular abnormalities in association with osteogenesis imperfecta and a COL1A1 mutation.

Abstract: A patient with osteogenesis imperfecta (OI) and some features of Ehlers-Danlos syndrome had Rieger's anomaly and other associated ocular abnormalities. He carried a COL1A1 mutation (c.3313delA) that has only rarely been seen in OI. The association of ocular anterior chamber abnormalities with OI has not been reported previously, while OI with Ehlers-Danlos syndrome features has only been described in some kindreds. The patient had serious complications as a result of his ocular anomalies. We speculate that the course of his disease and, perhaps, its co-existence with OI could be exacerbated by his collagen type-I defect, although no causality can be established by this report of a single case.

Ophthalmic aspects of GAPO syndrome: case report and review.

Abstract: This paper reports on a 36-year-old woman with GAPO syndrome, a rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Her parents are consanguineous and one of her sisters is also affected. Since the first description by Anderson and Pindborg in 1947, 27 individuals have been reported with this diagnosis. They were from at least 19 different families (four of them from Brazil, including the present one), suggesting a founder effect. The phenotype of this condition, initially considered as the result of an ectodermal dysplasia, could be attributed to the accumulation of extracellular connective tissue matrix and its progressive character must be pointed out. The clinical findings, especially ophthalmological features that include bilateral glaucoma, are reviewed and discussed.

Abnormal Distribution of Red/Green Cone Opsins in a Patient with an Autosomal Dominant Cone Dystrophy

Abstract: Purpose: To define the distribution of the red/green and blue opsins in cones from donor eyes from an affected member of a clinically well-characterized family with an autosomal dominant form of cone dystrophy. Methods: Tissue was fixed and processed for immunohistochemistry. Cryosections were studied by indirect immunofluorescence, using well-characterized antibodies to cone cytoplasm, rhodopsin, and cone opsins. The cone-associated matrix was also labeled with the lectin PNA. The affected donor eyes were compared to a postmortem matched normal eye. Results: Electroretinogram (ERG) testing three years prior to the affected member's death showed normal rod function, while the cone b-wave amplitude was reduced 40% below the lower limit of normal. Fundus exam showed only isolated drusen within the macula. Either a normal-appearing or only nonspecific macular findings were noted in the other affected family members who were examined. Immunofluorescence studies showed that blue cone opsin was restricted to th...

A new case of oculoectodermal syndrome.

Abstract: An 11-month-old infant girl presented with right-sided features of aplasia cutis congenita of the scalp, unilateral epibulbar dermoids, eccentric pupil, coloboma of the right upper eyelid, and depigmentation of the fundus surrounding the right optic nerve. These findings were similar to the oculoectodermal syndrome reported by other clinicians and researchers.

Coats-type retinal telangiectasia in case of Kabuki make-up syndrome (Niikawa-Kuroki syndrome).

Abstract: Purpose: To report a case of Kabuki make-up syndrome (KMS) or Niikawa-Kuroki syndrome with Coats-type retinal telangiectasia, which has not been previously reported. Methods: Observational case report. Conclusions: There have been only two reports of retinal pigmentation abnormalities and a single case of bilateral macular deposits in KMS, but this is the first report of a Coats type retinal telangiectasia. This case highlights the importance of thorough posterior segment examination in cases of KMS.

Bilateral complete isolated cryptophthalmos: a case report.

Abstract: Cryptophthalmos is a condition of congenital eyelid malformation most commonly accompanied by syndactyly, urogenital anomalies, and cognitive impairments as in Fraser syndrome. We report on a patient with characteristic features consistent with autosomal dominant bilateral complete isolated cryptophthalmos. This patient represents only the sixth documented case of bilateral complete isolated cryptophthalmos. Defining characteristics of this variety are discussed, including bilateral central dimpling over the globes, normal eyebrow growth, and the absence of cognitive impairment. We introduce phenotypic features that distinguish bilateral isolated cryptophthalmos from other forms and discuss its relatively favorable prognosis.

Molecular genetic and ocular findings in patients with holt-oram syndrome.

Abstract: Purpose: The autosomal dominant Holt-Oram syndrome (HOS) is characterized by upper limb and cardiac septal defects. Mutations of the TBX5 gene have been identified as the underlying gene defect in HOS. Embryonic expression of TBX5 has been found in the human retina. This is the first report of ocular findings in two unrelated families with mutations in the TBX5 gene. Methods: Six living persons affected with HOS and 10 unaffected family members were subjected to mutation analysis and complete ophthalmological examination, including electrophysiological examinations (EOG and flash ERG). Results: A heterozygous single base-pair substitution in exon 5 (408C → A) was detected in all affected patients. All examined affected patients were ophthalmologically asymptomatic with normal EOG. A scotopic elongated b-wave latency was found in affected family members who were older than 35 years. The ERG was normal in the younger patient. Conclusions: Haploinsufficiency of TBX5 alters the dorsal-ventral polarity in deve...

Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome

Abstract: Aarskog syndrome (faciogenital dysplasia) is an X-linked recessive genetic growth disorder characterized by short stature, dysmorphic facies, shawl scrotum, and digital anomalies. The condition was first described in 1970 and the gene responsible is FGD1 (MIM#305400). There are several reported ophthalmic findings associated with Aarskog syndrome which are discussed. We describe a case of Aarskog syndrome with venous tortuosity, optic nerve hypoplasia, and a type-2 antithrombin deficiency.

Association Down Syndrome-Retinoblatoma: A New Observation

Abstract: Dear Editor, A significant subset of cancers is due to a variety of constitutional genetic susceptibilities. The study of particular causative associations has allowed an understanding of the genet...

Mutation screen of the membrane-type frizzled-related protein (MFRP) gene in patients with inherited retinal degenerations.

Abstract: MFRP is a member of the frizzled-related protein family and contains a cysteine-rich domain essential for Wnt binding and signaling. MFRP is highly expressed in the retinal pigment epithelial cells of the eye. A splice donor mutation in the mouse ortholog of Mfrp is responsible for photoreceptor degeneration in the rd6 mouse. For these reasons, we investigated MFRP as a candidate gene for a phenotype associated with mutations. We screened 152 patients with inherited retinal degenerations including retinitis pigmentosa, Leber congenital amaurosis and Stargardt macular dystrophy. We identified five polymorphisms in the 5′ untranslated region, four missense changes, six isocoding variants and four intronic changes. None of the sequence variants were interpreted as pathogenic.

The coming of age for age-related macular degeneration genetics.

Abstract: Ophthalmic Genetics ISSN: 1381-6810 (Print) 1744-5094 (Online) Journal homepage: http://www.tandfonline.com/loi/iopg20 The Coming of Age for Age-Related Macular Degeneration Genetics Michael B. Gorin To cite this article: Michael B. Gorin (2005) The Coming of Age for Age-Related Macular Degeneration Genetics, Ophthalmic Genetics, 26:2, 57-59, DOI: 10.1080/13816810590969914 To link to this article: http://dx.doi.org/10.1080/13816810590969914 Published online: 08 Jul 2009. Submit your article to this journal Article views: 13 View related articles Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iopg20 Download by: [UCLA Library] Date: 11 April 2017, At: 12:47

Unilateral isolated microphthalmia inherited as an autosomal recessive trait.

Abstract: Purpose: To report a family with unilateral isolated microphthalmia showing an autosomal recessive pattern of inheritance. Case report: We report a family in which three out of four children, one male and monozygotic female twins, were born with unilateral isolated microphthalmia to healthy consanguineous parents. One twin additionally had a horseshoe kidney. Rare cases of familial isolated microphthalmia/anophthalmia have been previously described. This is the first report of a family with autosomal recessive isolated microphthalmia occurring unilaterally in all affected individuals. It remains unknown how this inherited genetic disease results in unilateral manifestation. Conclusion: Mirror imaging of this condition in the monozygotic twins may help elucidate the underlying mechanism. The constellation of features in this family may contribute to solve remaining questions of research into symmetry and asymmetry.

Retinoblastoma and Hypochondroplasia: A Case Report of Two Germline Mutations Arising Simultaneously

Abstract: Purpose: To report a rare case of a patient with two germline mutations arising de novo resulting in bilateral retinoblastoma and hypochondroplasia. Design: A brief review about retinoblastoma and hypochondroplasia; a case report with genetic mutational analysis results. Case report: We report a patient manifesting the clinical features of both bilateral retinoblastoma and hypochondroplasia. Genetic analysis revealed two germline mutations, a seven base-pair deletion in exon 12 (G70313-703129del) in one allele of the retinoblastoma gene (RB1) and the N540K (C1620C > A) mutation in one allele of the fibroblast growth factor 3 (FGFR3) gene, a frequent mutation in hypochondroplasia. Neither parent has a personal or family history of cancer or ocular tumors. Only the patient's mother is short in stature, and her genetic analysis revealed no FGFR3 mutations. Conclusions: Although the probability of both germline mutations occurring in a single individual is exceedingly low, the etiology and mechanism are unkno...