Mild form of oculocutaneous albinism type 1: phenotypic analysis of compound heterozygous patients with the R402Q variant of the <i>TYR</i> gene

Monfermé, Solène; Lasseaux, Eulalie; Duncombe-Poulet, C.; Hamel, C.; Defoort‐Dhellemmes, Sabine; Drumare, Isabelle; Zanlonghi, Xavier; Dollfus, Hélène; Perdomo, Yaurama; Bonneau, Dominique; Korobelnik, Jean‐François; Plaisant, Claudio; Michaud, Vincent; Pennamen, Perrine; Rooryck, Caroline; Morice‐Picard, Fanny; Paya, C.; Arveiler, Benoı̂t

doi:10.1136/bjophthalmol-2018-312729

Cited by 30 publications

(36 citation statements)

References 34 publications

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“…In this study, we intentionally selected subjects with albinism to represent a diverse sampling of albinism subtypes (see Table 1 ) in order to enhance the probability of observing variation in the central organization of visual pathways. Interestingly we saw disrupted central organization even in subjects with the recently described “tri-allelic” form of albinism ( Grønskov, Jespersgaard, Bruun, Harris, Brondum-Nielsen, Andresen, & Rosenberg, 2019 ; Monferme, Lasseaux, Duncombe-Poulet, Hamel, Defoort-Dhellemmes, Drumare, Zanlonghi, Dollfus, Perdomo, Bonneau, Korobelnik, Plaisant, Michaud, Pennamen, Rooryck-Thambo, Morice-Picard, Paya, & Arveiler, 2019 ; Norman, O'Gorman, Gibson, Pengelly, Baralle, Ratnayaka, Griffiths, Rose-Zerilli, Ranger, Bunyan, Lee, Page, Newall, Shawkat, Mattocks, Ward, Ennis, & Self, 2017 ). Although our sample is not nearly large enough to draw strong correlations among genetic, retinal, and central factors, we did observe variation across our albinism sample in the extent of hemifield overlap, pRF size, incidence of dual pRFs, and the distribution of dual pRFs across the visual field.…”

Section: Discussionmentioning

confidence: 58%

Aberrant visual population receptive fields in human albinism

et al. 2021

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Retinotopic organization is a fundamental feature of visual cortex thought to play a vital role in encoding spatial information. One important aspect of normal retinotopy is the representation of the right and left hemifields in contralateral visual cortex. However, in human albinism, many temporal retinal afferents decussate aberrantly at the optic chiasm resulting in partially superimposed representations of opposite hemifields in each hemisphere of visual cortex. Previous functional magnetic resonance imaging (fMRI) studies in human albinism suggest that the right and left hemifield representations are superimposed in a mirror-symmetric manner. This should produce imaging voxels which respond to two separate locations mirrored across the vertical meridian. However, it is not yet clear how retino-cortical miswiring in albinism manifests at the level of single voxel population receptive fields (pRFs). Here, we used pRF modeling to fit both single and dual pRF models to the visual responses of voxels in visual areas V1 to V3 of five subjects with albinism. We found that subjects with albinism (but not controls) have sizable clusters of voxels with unequivocal dual pRFs consistently corresponding to, but not fully coextensive with, regions of hemifield overlap. These dual pRFs were typically positioned at locations roughly mirrored across the vertical meridian and were uniquely clustered within a portion of the visual field for each subject.

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Section: Discussionmentioning

confidence: 58%

Aberrant visual population receptive fields in human albinism

et al. 2021

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“…OCA1 individuals often have no pigmentation at all, in the skin, hair, and eyes, but the variety of presentations is a continuous line from no signs of melanin to an almost normal pigmented phenotype, particularly associated with some TYR variants (e.g., R402Q) known to be thermosensitive, and whose pathogenicity has remained controversial for years (Lasseaux et al., 2018; Monfermé et al., 2019).…”

Section: Oculocutaneous Albinism Typementioning

confidence: 99%

Genetics of non‐syndromic and syndromic oculocutaneous albinism in human and mouse

Fernández

Hayashi

Garrido

et al. 2021

Pigment Cell Melanoma Res

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Oculocutaneous albinism (OCA) is the most frequent presentation of albinism, a heterogeneous rare genetic condition generally associated with variable alterations in pigmentation and with a profound visual impairment. There are non‐syndromic and syndromic types of OCA, depending on whether the gene product affected impairs essentially the function of melanosomes or, in addition, that of other lysosome‐related organelles (LROs), respectively. Syndromic OCA can be more severe and associated with additional systemic consequences, beyond pigmentation and vision alterations. In addition to OCA, albinism can also be presented without obvious skin and hair pigmentation alterations, in ocular albinism (OA), and a related genetic condition known as foveal hypoplasia, optic nerve decussation defects, and anterior segment dysgenesis (FHONDA). In this review, we will focus only in the genetics of skin pigmentation in OCA, both in human and mouse, updating our current knowledge on this subject.

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“…Illustratively, variants of the TYR gene responsible for oculocutaneous albinism type 1 (OCA1) can elicit either severe forms with a complete absence of pigmentation or forms with a pigmentation that appears normal, particularly in populations with a light phototype. Among 268 patients diagnosed with OCA1 in our recent study, 122 (45.5%) were compound heterozygotes for a known pathogenic TYR variant and the hypomorphic variant c.1205G>A/p.Arg402Gln (hereafter called R402Q) (Lasseaux et al, 2018 (Monfermé et al, 2019) showed that (i) this variant has a variable expressivity and displays incomplete penetrance; (ii) at the dermatologic level, most patients display a light phototype with residual pigmentation and a tendency to tan with age; the skin and hair can have a normally pigmented aspect; and (iii) at the ophthalmologic level, the classical ocular features of albinism are found, although photophobia and iris transillumination are less frequent, and severity scores are lower for various signs, such as foveal hypoplasia. The decrease of visual acuity is variable, ranging from very moderate to severe.…”

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confidence: 99%

“…a total lack of pigmentation. A þ nystagmus is described as micro-nystagmus by some authors (Monfermé et al, 2019). A þ foveal hypoplasia corresponds to grade 0 or 1 (almost normal fovea), whereas þþþþ corresponds to grade 4 (total absence of fovea) (Monfermé et al, 2019).…”

mentioning

confidence: 99%

“…A þ nystagmus is described as micro-nystagmus by some authors (Monfermé et al, 2019). A þ foveal hypoplasia corresponds to grade 0 or 1 (almost normal fovea), whereas þþþþ corresponds to grade 4 (total absence of fovea) (Monfermé et al, 2019). In HPS patients, variable severity of bleeding diathesis (ranging from moderate to severe platelet dysfunction), and/or of gastrointestinal (ranging from episodic abdominal pain to severe colic granulomatosis) and/or lung (absence or presence of variable degrees of respiratory failure, presence or absence of lung fibrosis) features can be observed.…”

mentioning

confidence: 99%

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