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Biomedical subjects

I H Maumenee

Publications and source records attributed to I H Maumenee.

At least 19 recordsLinked to original sources
PubMed1996

A gene for autosomal dominant congenital nystagmus localizes to 6p12.

Congenital nystagmus is an idiopathic disorder characterized by bilateral ocular oscillations usually manifest during infancy. Vision is typically decreased due to slippage of images across the fovea. As such, visual acuity correlates with nystagmus intensity, which is the amplitude and frequency of eye movements at a given position of gaze. X-linked, autosomal dominant, and autosomal recessive pedigrees have been described, but no mapping studies have been published. We recently described a large pedigree with autosomal dominant congenital nystagmus. A genome-wide search resulted in six markers on 6p linked by two-point analysis at theta = 0 (D6S459, D6S452, D6S465, FTHP1, D6S257, D6S430). Haplotype analysis localizes the gene for autosomal dominant congenital motor nystagmus to an 18-cM region between D6S271 and D6S455.

Chromosome Mapping↗
PubMed1996

The Castroviejo square graft.

The histopathologic features of three keratoplasty specimens from three cases involving square graft procedures performed by Dr. Castroviejo are reported. Light and electron microscopy were performed. In two of the cases, repeat keratoplasties were performed because of recurrent corneal dystrophies. In the third case, a repeat keratoplasty was performed because of graft failure.

Aged↗
PubMed1995

Immunohistochemical localization of fibrillin in human ocular tissues. Relevance to the Marfan syndrome.

OBJECTIVE: To better understand the ocular manifestations of the Marfan syndrome, we investigated the distribution of fibrillin in normal human ocular tissues. Fibrillin, a microfibrillar glycoprotein component of the extracellular matrix, has been found to be the defective gene product in the Marfan syndrome. METHODS: Frozen sections from seven pairs of normal eyes were stained with mouse anti-human fibrillin antibodies using the avidin-biotin immunoperoxidase technique. RESULTS: In the anterior segment, the following exhibited positive staining for fibrillin: the lens capsule and zonules; connective tissues of the iris, ciliary body, ciliary processes, and conjunctiva; and the basement membrane regions of the corneal epithelium and endothelium of Schlemm's canal. Posteriorly, fibrillin localized to the lamina cribrosa, sclera, choroid, and Bruch's membrane. CONCLUSIONS: Fibrillin is widely distributed in ocular connective tissues. The implications of defects in these tissues and the resultant ocular abnormalities in the Marfan syndrome such as ectopia lentis and glaucoma are discussed.

Aged↗
PubMed1995

Effects of strabismus surgery on refraction in children.

We assessed 115 eyes of 59 children with esotropia 2-3 months postoperatively to evaluate the effects of strabismus surgery on refraction. Three variables were measured: spherical equivalent, and cylinder power and axis. The mean changes in spherical equivalent were non-significant. The axis of postoperative astigmatism moved towards 'with-the-rule', thus improving refraction. The amount of recession and the consequent changes in cylinder power were inversely related. The results showed a significant change in cylinder axis after recession of the inferior oblique. Recession-tucking procedures led to the largest changes in cylinder power.

Astigmatism↗
PubMed1995

Photoaversion in Leber's congenital amaurosis.

Photoaversion is a prominent symptom of a number of infantile genetic ocular disorder such as congenital glaucoma, aniridia, albinism, and cone dystrophies including achromatopsia. Photoaversion has not been widely recognized as a clinical feature of Leber's congenital amaurosis. We present two patients who were diagnosed clinically with achromatopsia because of nystagmus, absent color vision, reduced visual acuity, and moderately severe photoaversion in the absence of anterior segment abnormalities. The photopic and scotopic responses of the electroretinogram (E R G) were nonrecordable in both patients indicating involvement of both cone and rod systems. The diagnosis was then revised to one of Leber's congenital amaurosis. Photoaversion can be a prominent clinical feature in some patients with Leber's congenital amaurosis. The E R G clinches the diagnosis. These patients may constitute a distinct genetic subtype of the disease and molecular genetic studies will help resolve this issue.

Blindness↗
PubMed1994

Strabismus in the Marfan syndrome.

We studied 573 patients with the Marfan syndrome for the presence of ocular misalignment, refractive errors, and amblyopia. A total of 110 patients (19.2%) had strabismus. Of 573 patients, exotropia occurred in 67 (11.7%), esotropia in 12 (2.1%), vertical deviations in eight (1.4%), and primary inferior oblique muscle overaction in three (0.5%). Of 67 patients with exotropia, 18 had anisometropia and 39 had amblyopia. Of the 12 patients with esotropia, four had amblyopia and none had anisometropia. Exotropia and esotropia are more common in patients with the Marfan syndrome than in the general population of the United States (P < .001 for exotropia and .05 < P < .10 for esotropia). Abnormal afferent visual inputs to cortical centers caused by ectopia lentis, craniofacial abnormalities, and mechanical and genetic factors may all contribute to the higher prevalence of strabismus in this disease.

Adolescent↗
PubMed1994

Ocular findings in trigonocephaly.

BACKGROUND: Trigonocephaly, caused by premature closure of the metopic suture, is a rare form of craniosynostosis. The aim of this study was to assess the visual outcome in children operated on for trigonocephaly. METHODS: We present eight cases of children with trigonocephaly surgically corrected by the same craniofacial technique. CT with 3D reconstruction was performed in all cases. Genitori defined three types of trigonocephaly according to the severity of the deformity of the skull base only types II and III were included in this study directed at evaluation of the ocular disorder. A complete eye examination was performed on all children by the same observer, with a follow-up of 2-6 years. RESULTS: 3D-CT reconstruction of the skull base showed that the frontozygomatic region was affected by the deformation. Ocular examination showed considerable astigmatism in most children with late operation. A low degree of strabismus was observed in most children. CONCLUSION: This study demonstrated that reconstructive surgery should be performed by the age of 6 months, given the immaturity of the visual system up to that time. Close cooperation between neurosurgeons, pediatricians and ophthalmologists is of paramount importance in order to prevent this bone deformation exerting an adverse effect on visual development. The ophthalmologist must possess a basic understanding of the various craniosynostoses.

Astigmatism↗
PubMed1994

Visual outcome after surgery for Peters' anomaly.

The authors reviewed the charts of 22 patients with Peters' anomaly. Various surgical procedures were performed on 30 eyes of 18 patients (mean number of procedures = 3.3 per eye). Follow-up averaged six years. Visual acuity varied widely, with six eyes having an acuity of 20/400 or better, and 11 eyes with no light perception. Concomitant or secondary glaucoma required a greater number of surgical procedures (4.1 vs 3.4) per eye and was associated with a poorer visual outcome. No eyes with glaucoma had visual acuity better than 20/400. In bilaterally operated patients, visual results in one eye were independent of the outcome of the fellow eye. The range of visual acuity in bilaterally operated patients was similar to the vision in those operated unilaterally. Visual outcome in patients with Peters' anomaly remains guarded. With modern surgical techniques and aggressive attempts at visual rehabilitation, many patients may benefit from surgery. Some patients may have moderately good visual acuity for months or years before vision is lost. In the interim they may learn tasks they may not have otherwise acquired.

Cataract Extraction↗
PubMed1993

Visual prognosis in autosomal dominant optic atrophy (Kjer type).

We examined 25 patients from three pedigrees with dominant optic atrophy (Kjer type). Follow-up on 20 patients ranged from five to 40 years (mean, 16 years; median, 13 years). Visual acuity ranged from 20/20 (in one 58-year-old man with an affected father and three affected children) to 20/400. The median initial visual acuity was 20/60, and the median final visual acuity was 20/80. Visual acuity remained unchanged or decreased by one Snellen line in both eyes of 13 patients (65%); it decreased between two and four Snellen lines in only one eye in three patients (15%) and in both eyes in four patients (20%). The rate of visual loss was unrelated to initial visual acuity or the particular pedigree to which the patient belonged. There was functional and ophthalmoscopic heterogeneity between and within the pedigrees. Eight patients perceived moderate to severe social or occupational handicap. Visual prognosis is relatively good in Kjer's dominant optic atrophy with stable or slow progression of visual loss.

Adolescent↗
PubMed1993

Anterior segment malformations in 18q- (de Grouchy) syndrome.

The authors examined two patients with deletions of the terminal end of the long arm of chromosome 18. The ocular findings in one patient with 46, XX, del 18 (q21) consisted of hypertelorism, epicanthus, strabismus, myopia, microphthalmia, microcornea, corneal opacities, iris hypoplasia with full thickness defects, corectopia and large peripapillary staphylomata. The second patient with 46, XX, del (18) (pter --> q21.2 :: q22 --> qter), inv (21) (q21 --> p12 :: q21 --> qter) only had epicanthus, strabismus, myopia and peripapillary crescents. Based on the findings in these two patients and on a review of previously reported patients with del 18 qter it appears that the loss of band 18q23 may be responsible for malformations of the anterior segment in the 18q-syndrome.

Anterior Eye Segment↗
PubMed1993

[Possible origins of the gene of Hermansky-Pudlak in Puerto Rico].

Five out of six albino persons in Puerto Rico suffer from the Hermansky-Pudlak syndrome. This syndrome has been reported also in other countries such as Great Britain, the Netherlands, Belgium, and Mexico, among others. Due to the geographical isolation of the island it is likely that these patients share a common ancestor. In explaining how the gene may have arrived to Puerto Rico the following possibilities are considered: (1) British soldiers attacking the island since 1595. (2) Dutch attackers in 1625. (3) aboriginal tribes. (4) slave traders.

Albinism, Oculocutaneous↗
PubMed1993

Genetic heterogeneity among blue-cone monochromats.

Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.

Base Sequence↗
PubMed1993

Identification of novel rhodopsin mutations responsible for retinitis pigmentosa: implications for the structure and function of rhodopsin.

Ten rhodopsin mutations have been found in a screen of 282 subjects with retinitis pigmentosa (RP), 76 subjects with Leber congenital amaurosis, and 3 subjects with congenital stationary night blindness. Eight of these mutations (gly51-to-ala, val104-to-ile, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, val209-to-met, and his211-to-arg) produce amino acid substitutions, one (gln64-to-ter) introduces a stop codon, and one changes a guanosine in the intron 4 consensus splice donor sequence to thymidine. Cosegregation of RP with gln64-to-ter, gly106-to-arg, arg135-to-gly, cys140-to-ser, gly188-to-glu, his211-to-arg, and the splice site guanosine-to-thymidine indicates that these mutations are likely to cause retinal disease. Val104-to-ile does not cosegregate and is therefore unlikely to be related to retinal disease. The relevance of gly51-to-ala and val209-to-met remains to be determined. The finding of gln64-to-ter in a family with autosomal dominant RP is in contrast to a recent report of a recessive disease phenotype associated with the rhodopsin mutation glu249-to-ter. In the present screen, all of the mutations that cosegregate with retinal disease were found among patients with RP. The mutations described here bring to 35 the total number of amino acid substitutions identified thus far in rhodopsin that are associated with RP. The distribution of the substitutions along the polypeptide chain is significantly nonrandom: 63% of the substitutions involve those 19% of amino acids that are identical among vertebrate visual pigments sequenced to date.

Alleles↗
PubMed1992

Ocular findings in Cockayne syndrome.

The ocular findings in eight patients with Cockayne syndrome included enophthalmos, hyperopia, poor pupillary dilation, and retinal dystrophy in all patients. Four patients had strabismus. Two patients had cataracts. Three patients had nystagmus. Visual acuity was relatively well preserved in six patients, including a 25-year-old man with a visual acuity of 20/60 in each eye despite advanced retinal pigmentary changes. Failure of DNA and RNA synthesis to recover after ultraviolet light exposure as well as selective loss of repair of transcriptionally active DNA may account for the ocular abnormality in this progeric syndrome.

Adult↗
PubMed1992

Ocular histopathologic characteristics of cobalamin C type vitamin B12 defect with methylmalonic aciduria and homocystinuria.

The eyes of a 22-month-old girl with the cobalamin C complementation type of combined methylmalonic aciduria and homocystinuria were studied with light and electron microscopy. We observed vacuolization of the iris pigment epithelium, loss of photoreceptors in the central 3.3 mm of the macula, partial loss of the nerve fiber and ganglion cell layers between the fovea and optic disk, and partial optic atrophy. The sclera in the posterior pole was thickened with deposition of mucopolysaccharide. Electron microscopy showed inclusions containing fine granular material in conjunctival fibrocytes; corneal epithelium, keratocytes, and endothelial cells; iris pigment epithelium; ganglion cells; retinal pigment epithelium; and choroid and scleral fibrocytes. Enlarged mitochondria and clear vacuoles distended the corneal endothelial cells. We found evidence of possible lysosomal dysfunction and mucopolysaccharide storage, as well as a clinicopathologic correlation of the macular degeneration in this disease.

Eye↗
PubMed1992

Mitochondrial DNA mutation and heteroplasmy in type I Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by bilateral acute or subacute loss of central vision, primarily in young males. A G----A single base mutation at 11778nt of the mitochondrial genome which eliminates a SfaNI restriction site [Wallace et al., 1988; Holt et al., 1989; Hotta et al., 1989; Singh et al., 1989; Vilkki et al., 1989; Yoneda et al., 1989; Stone et al., 1990; Lott et al., 1990.] has been found in more than 60% of the families with LHON studied. We studied 25 persons from 4 families with LHON using SfaNI and Mae III digestion of a 201 base pair polymerase chain reaction (PCR) product encompassing the 11778nt mutation. The loss of the SfaNI site and the acquisition of a Mae III site at 11778nt were identified in all maternal relatives of the LHON families studied. The mutation was heteroplasmic in all affected individuals, female carriers, and males at-risk. The heteroplasmy of mitochondrial DNA (mtDNA) was also identified by direct DNA sequencing of PCR amplified by direct DNA sequencing of PCR amplified mtDNA digested by SfaNI or Mae III. It appears that the proportion of the mutant mtDNA correlates with the severity of the disease.

Adenine↗
PubMed1992

Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes.

Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.

Adolescent↗