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At least 199 records · Page 11Linked to original sources
PubMed2000

Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.

Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by a severe reduction of visual acuity, hypopigmentation of the retina and the presence of macromelanosomes in the skin and eyes. Various types of mutation have been identified within the OA1 gene in patients with the disorder, including several missense mutations of unknown functional significance. In order to shed light into the molecular pathogenesis of ocular albinism and possibly define critical functional domains within the OA1 protein, we characterized 19 independent missense mutations with respect to processing and subcellular distribution on expression in COS-7 cells. Our analysis indicates the presence of at least two distinct biochemical defects associated with the different missense mutations. Eleven of the nineteen OA1 mutants (approximately 60%) were retained in the endoplasmic reticulum, showing defecNStive intracellular transport and glycosylation, consistent with protein misfolding. The remaining eight of the nineteen OA1 mutants (approximately 40%) displayed sorting and processing behaviours indistinguishable from those of the wild-type protein. Consistent with our recent findings that OA1 represents a novel type of intracellular G protein-coupled receptor (GPCR), we found that most of these latter mutations cluster within the second and third cytosolic loops, two regions that in canonical GPCRs are known to be critical for their downstream signaling, including G protein-coupling and effector activation. The biochemical analysis of OA1 mutations performed in this study provides important insights into the structure-function relationships of the OA1 protein and implies protein misfolding as a major pathogenic mechanism in OA1.

Albinism, Ocular↗
PubMedDate not supplied

Mottled coloration in a rainbow trout is associated with mosaicism for albinism.

Within a group of rainbow trout at a commercial farm, a single individual was noted for its mottled yellow and dark skin pigmentation. This female fish was reared to sexual maturity and sublots of its eggs were crossed to rainbow trout males from golden, albino, and wild-type (dark-pigmented) strains. Development in other eggs was activated to produce diploid gynogenetic offspring. Coloration within each progeny group was scored at 10 weeks following initiation of feeding. Mottled coloration was observed in none of the progeny at this time. The phenotypes observed (palomino, albino, and/or wild type) and their proportions within progeny groups indicated that the mottled female was originally heterozygous for albinism. The fish apparently became mosaic for this trait following mutation of the wild-type allele at the albinism locus within a cell(s) early in embryonic development. Curiously, at approximately 6 months after initiation of feeding, mottled coloration became apparent in 2 fish from among 25 progeny of the cross to the golden male. No change in phenotype was noted at this time in 9 gynogenetic progeny nor in 68 progeny from the cross to the albino male. Apparently additional mutations and/or other genetic and regulatory processes affecting coloration came into play during juvenile development of these latter two fish.

Albinism↗
PubMedDate not supplied

Albinism and its inheritance in populations of the montane vole.

Albinism was observed in natural populations of the montane vole, Microtus montanus nanus, in Grand Teton National Park, Wyoming. Two individuals, apparently littermates, were captured in a high density population in 1976, and a third was taken at the same site from a high density population one year later. Laboratory breeding tests established that albinism in this species is inherited as an autosomal homozygous recessive. Territorial polygyny and the occurrence of extended maternal families at high densities may result in significant amounts of inbreeding as evidenced by presumably maladaptive homozygous recessive pelage variants such as albino.

Albinism↗
PubMed1985

Histopathologic evaluation of melanocytic nervi in oculocutaneous albinism.

This is a report of the histopathologic findings of melanocytic nevi in patients with oculocutaneous albinism. Seven albino patients, four tyrosinase positive and three tyrosinase negative, with a total of 34 melanocytic lesions were available for examination. The specimens were examined histopathologically for the presence of intranuclear pseudoinclusions, giant melanocytic cells, eosinophilic globules, features of congenital nevi, and atypical changes. A statistically significant increased number of giant melanocytic cells were found in intradermal nevi (p less than 0.0025), compound nevi (p less than 0.01), and junctional nevi of the patients with albinism compared with controls. Eosinophilic globules were found in 17% of the 34 nevi, and congenital features in 8.8%. All lesions showed adequate maturation of cells with no atypical changes. Marked solar elastosis was found in the dermis around and beneath the nevi, even though most lesions were in covered areas.

Adult↗
PubMed1983

Prenatal diagnosis of oculocutaneous albinism by electron microscopy of fetal skin.

Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis.

Adult↗
PubMed1992

Do pigmented naevi in albinism provide evidence of tyrosinase positivity?

We investigated a 4-year-old Japanese boy with oculocutaneous albinism who had a solitary pigmented mole measuring 5 mm in diameter on his back. An electron microscopic tyrosine incubation test and a DOPA reaction test clearly demonstrated the presence of tyrosinase activity in the patient's hypopigmented skin. The presence of tyrosinase activity was confirmed by tests on hair bulb samples. Histopathological evidence showed that the mole was a typical compound cellular naevus with melanin pigmentation. Although no reports to date have focused on the relationship between pigmented naevi in albinism and tyrosinase activity, our findings suggest that the occurrence of pigmented naevi in an albino may indicate the presence of tyrosinase activity.

Albinism↗
PubMed1980

Macromelanosomes in X-linked ocular albinism.

Examination of clinically normal skin from four patients with X-linked ocular albinism of the Nettleship-Falls type by light and electron microscopy revealed the presence of macromelanosomes in some melanocytes and keratinocytes. Measuring up to 5 micron many of the abnormal melanosomes showed a concentrically laminated structure suggestive of a phasic growth pattern. Epidermis from three female carriers contained similar but fewer macromelanosomes. These findings indicate that skin biopsy could be of value not only in confirming the diagnosis of ocular albinism in affected males, but also to establish carrier status in asymptomatic females.

Albinism↗
PubMed1980

Albinism in Nigeria with delineation of new recessive oculocutaneous type.

Seventy-nine Nigerian oculocutaneous albinos were investigated. Fifty-six had typical tyrosinase-positive albinism (TPA) and 23 had brown albinism (BA), a new oculocutaneous type. The TPA were characterized by localized but no generalized skin pigment, yellow hair, blue to brown irides, nystagmus, and reduced or absent retinal pigment. Localized skin pigment included freckles and lentigines. The iris and skin pigment were the result of the slow accumulation of pigment with age as both were found in older individuals. The most severe skin changes were premalignant keratoses and squamous cell carcinoma of the skin, and the skin malignancies were the major factor in limiting the lifespan for TPA. The BA were characterized by generalized light brown skin pigment, light brown hair, blue to brown irides, nystagmus, and reduced retinal pigment. There was little accumulation or change of pigment in the eyes or skin with age. The generalized light skin pigment was effective in reducing sensitivity to solar radiation and very few BA had premalignant keratoses. Pedigree analysis for BA suggested on autosomal recessive inheritance pattern.

Adolescent↗
PubMed1980

Forsius-Eriksson syndrome: its relation to the Nettleship-Falls X-linked ocular albinism.

On the basis of clinical data, it had previously been proposed that the Forsius-Eriksson syndrome is identical to Nettleship-Falls X-linked ocular albinism. We performed biopsies of clinically-normal skin in patients with the Forsius-Eriksson syndrome to look for the abnormal melanosomes characteristic of Nettleship-Falls X-linked ocular albinism. There were no abnormalities in the melanosomes of patients with Forsius-Eriksson syndrome. Thus, this syndrome is distinct from the Nettleship-Falls disorder.

Albinism↗
PubMed1987

Cerebellar ataxia and total albinism.

In this report a family is described where cerebellar ataxia occurred along with total albinism. A possibility of syntenic condition of the two genes responsible for the traits could explain the occurrence of the two conditions. The presence of two traits singly in the sibs reflects a recombinant event and suggests that the linkage is not absolute. Chromosomal study did not show any structural or numerical anomalies except in 1/50 metaphase plates scored in the proband (with cerebellar ataxia) where in chromosome No. 14 proximal intense band (21) seemed to be shifted, inv. (14) (q13q23?). The affected sibs with ataxia and albinism or ataxia alone depicted relatively a lower sister chromatid exchange (SCE) rate than their parents and age matched controls.

Albinism↗
PubMed2004

A transgenic mouse model with inducible Tyrosinase gene expression using the tetracycline (Tet-on) system allows regulated rescue of abnormal chiasmatic projections found in albinism.

Congenital defects in retinal pigmentation, as in oculocutaneous albinism Type I (OCA1), where tyrosinase is defective, result in visual abnormalities affecting the retina and pathways into the brain. Transgenic animals expressing a functional tyrosinase gene on an albino genetic background display a correction of all these abnormalities, implicating a functional role for tyrosinase in normal retinal development. To address the function of tyrosinase in the development of the mammalian visual system, we have generated a transgenic mouse model with inducible expression of the tyrosinase gene using the tetracycline (TET-ON) system. We have produced two types of transgenic mice: first, mice expressing the transactivator rtTA chimeric protein under the control of mouse tyrosinase promoter and its locus control region (LCR), and; second, transgenic mice expressing a mouse tyrosinase cDNA construct driven by a minimal promoter inducible by rtTA in the presence of doxycycline. Inducible experiments have been carried out with selected double transgenic mouse lines. Tyrosinase expression has been induced from early embryo development and its impact assessed with histological and biochemical methods in heterozygous and homozygous double transgenic individuals. We have found an increase of tyrosinase activity in the eyes of induced animals, compared with littermate controls. However, there was significant variability in the activation of this gene, as reported in analogous experiments. In spite of this, we could observe corrected uncrossed chiasmatic pathways, decreased in albinism, in animals induced from their first gestational week. These mice could be instrumental in revealing the role of tyrosinase in mammalian visual development.

Albinism, Oculocutaneous↗
PubMed2005

Reversion mutation of ib oculocutaneous albinism to wild-type pigmentation in medaka fish.

We have previously identified three naturally occurring mutations in the medaka fish tyrosinase gene caused by transposable element insertions. Tyr-i(b) is one of these, containing the Tol2 element in the promoter region. Its homozygous carriers exhibit a weak oculocutaneous albino phenotype. We report here spontaneous reversion of the albino phenotype to the wild-type pigmentation, associated with excision of the Tol2 element. The newly arising mutant gene is inherited in the Mendelian fashion. Thus, oculocutaneous albinism is not strictly irreversible, at least in this organism and the results also indicate that the insertion of the Tol2 element is the main, and possibly the only, cause of the i(b) albinism. Importantly our data also suggest that medaka fish possess an active transposase.

Albinism, Oculocutaneous↗
PubMed2006

Oculocutaneous albinism with TYRP1 gene mutations in a Caucasian patient.

Non-syndromic oculocutaneous albinism (OCA) is a clinically and genetically heterogeneous autosomal recessive disorder with mutations identified in several genes: OCA1 (tyrosinase, TYR), OCA2 (OCA2), OCA3 (tyrosinase-related protein 1, TYRP1), and OCA4 (membrane-associated transporter protein, MATP). OCA3 was thought to be restricted to black populations, where it was clinically described as rufous or brown albinism, until the recent report of a homozygous TYRP1 mutation in Caucasian patients from a consanguineous Pakistani family. Here, we describe a German patient of Caucasian origin, with a light-yellow skin, yellow-gold hair with orange highlights, fair eyelashes, several pigmented naevi, and no tendency to tan, only to burn. Eye-colour is blue-green with substance defects of the iris. Molecular analysis did not reveal any mutation in the TYR and OCA2 genes. Two mutations were found in the TYRP1 gene: a missense mutation (c.1066G>A/p.Arg356Glu) that was inherited from the mother, and a de novo single-base deletion (c.106delT/p.Leu36X). This finding suggests that mutation screening should be extended to the TYRP1 gene in patients from all ethnic origins, at least in cases where no mutations have been identified in the other OCA genes.

Albinism, Oculocutaneous↗
PubMed1990

Albinism in childhood: a flash VEP and ERG study.

Flash visual evoked potentials (F. VEPs) and electroretinograms (ERGs) were recorded in a total of 20 young children with albinism (age range 5 months to 11 years, mean 4 years). All recordings were made without sedation. There were 13 oculocutaneous cases (one with Hermansky-Pudlak syndrome) and seven ocular albinos. Monocular flash stimulation commonly elicited an asymmetrical occipital VEP distribution with a well lateralised component at around 80 ms which was of opposite polarity in a comparison of VEPs from each eye. None of the normally pigmented matched controls or obligate female carriers showed this anomalous distribution. The albino electroretinogram, compared with controls, recorded under fully darkened conditions had a significantly larger a wave and significantly shorter latencies for both a and b waves. The accentuated ERG and asymmetrical VEP recorded in infants and young children with albinism permits distinction of these patients from those with congenital cone dysfunction and idiopathic nystagmus, with whom they may be confused by a clinical examination only.

Albinism↗
PubMed1996

Transillumination of iris and subnormal visual acuity--ocular albinism?

BACKGROUND: A common clinical sign in children with subnormal visual acuity or slow visual development was iris transillumination. This was used as the inclusion criterion in a study of children shown to have a subnormal visual acuity in a general health examination at age 4 years. METHODS: Refraction values, stereopsis, fundus photography, macular and nerve head appearance, and visual evoked response (VER) recordings were studied in 18 children. The clinical results were compared with 64 controls referred to the eye clinic because of subnormal vision from the general health examination or from school health care. RESULTS: Eight children had VERs showing asymmetry typical for albinism. Another four had only small asymmetries on the VER, indicating a lower degree of decussation abnormality. No simple correlation of visual acuity, degree of iris transillumination, stereopsis, or macular pathology and VER asymmetries were found. However, marked iris transillumination in all four quadrants, absence of a foveal reflex, and low visual acuity were weakly correlated. CONCLUSIONS: In a rather homogeneous group of children with iris transillumination and subnormal visual acuity eight of 18 had typical albino VERs. The findings of small atypical VER asymmetries in four children and no asymmetry in six children suggest that albinism may be considered as a description of a heterogeneous group of conditions including maximal decussation rate (100%) in the chiasma to a condition with almost normal (> or = 50%) decussation rate.

Adolescent↗
PubMed1988

Visual evoked potentials in Negro carriers of the gene for tyrosinase positive oculocutaneous albinism.

Visual evoked potential testing was performed on 15 Negro carriers of the gene for tyrosinase positive oculocutaneous albinism in order to detect whether they have the same visual pathway decussation anomalies as do homozygotes. No subject showed 01-02 asymmetry on monocular testing, indicating that decussation follows the normal pattern. It is concluded that visual evoked potential testing is probably not useful in the detection of Negroes heterozygous for the gene for tyrosinase positive oculocutaneous albinism.

Adolescent↗
PubMed1993

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.

Abnormalities, Multiple↗