Clinical and genetic variability in children with partial albinism

Campbell, Patrick; Ellingford, Jamie M; Parry, Neil R. A.; Fletcher, Tracy; Ramsden, Simon; Gale, Theodora; Hall, Georgina; Smith, Katherine R.; Kasperavičiūtė, Dalia; Thomas, E. R. A.; Lloyd, Iva; Douzgou, Sofia; Clayton‐Smith, Jill; Biswas, Susmito; Ashworth, Jane; Black, Graeme C M; Sergouniotis, Panagiotis I.

doi:10.1038/s41598-019-51768-8

Cited by 38 publications

(45 citation statements)

References 55 publications

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“…This data is in line with literature reporting no pathognomonic features for OA. 20 The longitudinal evaluation of our sample revealed unchanged ocular and oculomotor signs, a deficit in visual acuity that progressively improved and a complete recovery in contrast sensitivity. The level of visual acuity and its improvement are similar to those observed in previous studies on albino patients 21,22 and are lower than published age-based population norms.…”

Section: Discussionmentioning

confidence: 64%

Neurodevelopmental Profile in Children Affected by Ocular Albinism

et al. 2021

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Aim The aim of this study was to detail the neurodevelopmental profile of subjects affected by ocular albinism (OA) and to collect data on GPR143 gene analysis. Design The design of the study involves a retrospective longitudinal observational case series. Methods We collected data on the neurodevelopmental profile of 13 children affected by OA from clinical annual assessments conducted for a period of 6 years after the first evaluation. We described visual profile, neuromotor development and neurological examination, cognitive profile, communication and language skills and behavioral characteristics. The GPR143 gene analysis was performed as well. Results Children presented a variable combination of ocular and oculomotor disorders unchanged during the follow-up, a deficit in visual acuity and in contrast sensitivity that progressively improved. Abnormalities in pattern visual evoked potential were found. No deficits were detected at neurological examination and neuromotor development except for a mild impairment in hand-eye coordination observed in five cases. A language delay was observed in five cases, two of whom had also a developmental quotient delay at 2 years evolving to a borderline/deficit cognitive level at preschool age, difficulties in adaptive behavior and autistic-like features were found. Mutations in the GPR143 gene were identified in the two patients who presented the most severe clinical phenotype. Conclusion Children with OA may share, in addition to a variable combination of ocular signs and symptoms, a neurodevelopment impairment regarding mostly the cognitive, communicative, and social area, especially those with GPR143 mutation.

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Section: Discussionmentioning

confidence: 64%

Neurodevelopmental Profile in Children Affected by Ocular Albinism

et al. 2021

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“…The presence of these variants and the OCA2 143kb;184kb CxSV in one individual indicates that heterozygosity for a combination of deleterious variants in multiple genes may represent a polygenic cause of OCA. Compound heterozygosity for OCA‐associated variants has been previously proposed for other albinism patients (Campbell et al, 2019; Hutton & Spritz, 2008).…”

Section: Resultsmentioning

confidence: 91%

A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the OCA2 locus

et al. 2021

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Oculocutaneous albinism (OCA) is a heritable disorder of pigment production that manifests as hypopigmentation and altered eye development. Exon sequencing of known OCA genes is unsuccessful in producing a complete molecular diagnosis for a significant number of affected individuals. We sequenced the DNA of individuals with OCA using short‐read custom capture sequencing that targeted coding, intronic, and noncoding regulatory regions of known OCA genes, and genome‐wide association study‐associated pigmentation loci. We identified an OCA2 complex structural variant (CxSV), defined by a 143 kb inverted segment reintroduced in intron 1, upstream of the native location. The corresponding CxSV junctions were observed in 11/390 probands screened. The 143 kb CxSV presents in one family as a copy number variant duplication for the 143 kb region. In the remaining 10/11 families, the 143 kb CxSV acquired an additional 184 kb deletion across the same region, restoring exons 3–19 of OCA2 to a copy‐number neutral state. Allele‐associated haplotype analysis found rare SNVs rs374519281 and rs139696407 are linked with the 143 kb CxSV in both OCA2 alleles. For individuals in which customary molecular evaluation does not reveal a biallelic OCA diagnosis, we recommend preliminary screening for these haplotype‐associated rare variants, followed by junction‐specific validation for the OCA2 143 kb CxSV.

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“…The OCA4 phenotype of patients P1, P2, and P3 seems the very opposite of the phenotype of the FHONDA syndrome, caused by mutations in SLC38A8 42,43,44,45 . Patients with FHONDA have nystagmus, poor VA, severe foveal hypoplasia and misrouting, but no pigmentation defect.…”

Section: Discussionmentioning

confidence: 87%

An Unusual Phenotype in Dutch Patients With Oculocutaneous Albinism Type 4: Evident Hypopigmentation Without Other Ocular Deficits.

Kruijt

Schalij‐Delfos

Wit

et al. 2021

Preprint

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Purpose: To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4).Patients and Methods: We collected data on pigmentation (skin, hair, and eyes), visual acuity (VA), nystagmus, foveal hypoplasia, chiasmal misrouting, and molecular analyses of nine Dutch OCA4 patients from the Bartiméus Diagnostic Center for complex visual disorders.Results: All patients had severely reduced pigmentation of skin, hair, and eyes with iris transillumination over 360 degrees. Three unrelated OCA4 patients had normal VA, no nystagmus, no foveal hypoplasia, and no misrouting of the visual pathways. Six patients had poor visual acuity (0.6 to 1.0 logMAR), nystagmus, severe foveal hypoplasia and misrouting. We found two novel mutations in the SLC45A2 gene, c.310C>T; p.(Pro104Ser), and c.1368+3_1368+9del p.(?).Discussion: OCA4 patients of this Dutch cohort all had hypopigmentation of skin, hair, and iris translucency. However, patients were either severely affected with regard to visual acuity, foveal hypoplasia, and misrouting, or visually not affected at all. We describe for the first time OCA4 patients with an evident lack of pigmentation, but normal visual acuity, normal foveal development and absence of misrouting. This implies that absence of melanin does not invariably lead to foveal hypoplasia and abnormal routing of the visual pathways.

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Clinical and genetic variability in children with partial albinism

Cited by 38 publications

References 55 publications

Neurodevelopmental Profile in Children Affected by Ocular Albinism

Neurodevelopmental Profile in Children Affected by Ocular Albinism

A custom capture sequence approach for oculocutaneous albinism identifies structural variant alleles at the OCA2 locus

An Unusual Phenotype in Dutch Patients With Oculocutaneous Albinism Type 4: Evident Hypopigmentation Without Other Ocular Deficits.

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