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Article ; Online: Albinism: An Underdiagnosed Condition.

Arveiler, Benoit / Michaud, Vincent / Lasseaux, Eulalie

The Journal of investigative dermatology

2019 Volume 140, Issue 7, Page(s) 1449–1451

MeSH term(s)	Albinism, Oculocutaneous/diagnosis ; Albinism, Oculocutaneous/genetics ; Diagnosis, Differential ; Female ; Heterozygote ; Humans ; Molecular Diagnostic Techniques ; Ophthalmology ; Phenotype ; Pregnancy ; Prenatal Diagnosis ; Syndrome
Language	English
Publishing date	2019-12-26
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2019.12.010
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Article ; Online: Genotypic spectrum of albinism in Mali.

Diallo, Modibo / Sylla, Ousmane / Sidibé, Mohamed Kole / Plaisant, Claudio / Mercier, Elina / Sequeira, Angèle / Javerzat, Sophie / Hadid, Abdelaziz / Lasseaux, Eulalie / Michaud, Vincent / Arveiler, Benoit

Pigment cell & melanoma research

2024

Abstract: Albinism is a phenotypically and genetically heterogeneous condition characterized by a variable degree of hypopigmentation and by ocular features leading to reduced visual acuity. Whereas numerous genotypic studies have been conducted throughout the ... ...

Abstract	Albinism is a phenotypically and genetically heterogeneous condition characterized by a variable degree of hypopigmentation and by ocular features leading to reduced visual acuity. Whereas numerous genotypic studies have been conducted throughout the world, very little is known about the genotypic spectrum of albinism in Africa and especially in sub-Saharan Western Africa. Here we report the analysis of all known albinism genes in a series a 23 patients originating from Mali. Four were diagnosed with OCA 1 (oculocutaneous albinism type 1), 17 with OCA 2, and two with OCA 4. OCA2 variant NM_000275.3:c.819_822delinsGGTC was most frequently encountered. Four novel variants were identified (two in TYR, two in OCA2). A deep intronic variant was found to alter splicing of the OCA2 RNA by inclusion of a pseudo exon. Of note, the OCA2 exon 7 deletion commonly found in eastern, central, and southern Africa was absent from this series. African patients with OCA 1 and OCA 4 had only been reported twice and once, respectively, in previous publications. This study constitutes the first report of the genotypic spectrum of albinism in a western sub-Saharan country.
Language	English
Publishing date	2024-05-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2409570-9
ISSN	1755-148X ; 1600-0749 ; 0893-5785 ; 1755-1471
ISSN (online)	1755-148X ; 1600-0749
ISSN	0893-5785 ; 1755-1471
DOI	10.1111/pcmr.13175
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Article ; Online: Proteome characterization of XPC-deficient melanocytes generated by CRISPR-Cas9 technology reveals alteration in the expression of several hundred proteins.

Cario, Muriel / Scalia, Julie / Mahfouf, Walid / Muzotte, Elodie / Michaud, Vincent / Plaisant, Claudio / Dupuy, Jean-William / Douki, Thierry / Morice-Picard, Fanny / Rambert, Jérôme / Perrier, Eric / Trompezinski, Sandra / Rezvani, Hamid-Reza

Journal of dermatological science

2024

Language	English
Publishing date	2024-03-23
Publishing country	Netherlands
Document type	Letter
ZDB-ID	1024446-3
ISSN	1873-569X ; 0923-1811
ISSN (online)	1873-569X
ISSN	0923-1811
DOI	10.1016/j.jdermsci.2024.03.006
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Article ; Online: Whole-exome sequencing confirms implication of VPS13D as a potential cause of progressive spastic ataxia.

Durand, Christelle M / Angelini, Chloé / Michaud, Vincent / Delleci, Claire / Coupry, Isabelle / Goizet, Cyril / Trimouille, Aurelien

BMC neurology

2022 Volume 22, Issue 1, Page(s) 53

Abstract: Background: VPS13D is a large ubiquitin-binding protein playing an essential role in mitophagy by regulating mitochondrial fission. Recently, VPS13D biallelic pathogenic variants have been reported in patients displaying variable neurological phenotypes, ...

Abstract	Background: VPS13D is a large ubiquitin-binding protein playing an essential role in mitophagy by regulating mitochondrial fission. Recently, VPS13D biallelic pathogenic variants have been reported in patients displaying variable neurological phenotypes, with an autosomic recessive inheritance. The objectives of the study were to determine the genetic etiology of a patient with early onset sporadic progressive spastic ataxia, and to investigate the pathogenicity of VPS13D variants through functional studies on patient's skin fibroblasts. Case presentation: We report the case of a 51-year-old patient with spastic ataxia, with an acute onset of the disease at age 7. Walking difficulties slowly worsened over time, with the use of a wheelchair since age 26. We have used trio-based whole-exome sequencing (WES) to identify genes associated with spastic ataxia. The impact of the identified variants on mitochondrial function was assessed in patient's fibroblasts by imaging mitochondrial network and measuring level of individual OXPHOS complex subunits. Compound heterozygous variants were identified in VPS13D: c.946C > T, p.Arg316* and c.12416C > T, p.(Ala4139Val). Primary fibroblasts obtained from this patient revealed an altered mitochondrial morphology, and a decrease in levels of proteins from complex I, III and IV. Conclusions: Our findings confirmed implication of VPS13D in spastic ataxia and provided further support for mitochondrial defects in patient's skin fibroblasts with VPS13D variants. This report of long-term follow up showed a slowly progressive course of the spastic paraplegia with cerebellar features. Furthermore, the performed functional studies could be used as biomarker helping diagnosis of VPS13D-related neurological disorders when molecular results are uneasy to interpret.
MeSH term(s)	Adult ; Child ; Humans ; Intellectual Disability ; Middle Aged ; Muscle Spasticity ; Mutation ; Optic Atrophy ; Pedigree ; Phenotype ; Proteins ; Spastic Paraplegia, Hereditary/genetics ; Spinocerebellar Ataxias/genetics ; Whole Exome Sequencing
Chemical Substances	Proteins ; VPS13D protein, human
Language	English
Publishing date	2022-02-12
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2041347-6
ISSN	1471-2377 ; 1471-2377
ISSN (online)	1471-2377
ISSN	1471-2377
DOI	10.1186/s12883-022-02553-0
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Article ; Online: Aminoacylation-defective bi-allelic mutations in human EPRS1 associated with psychomotor developmental delay, epilepsy, and deafness.

Jin, Danni / Wek, Sheree A / Cordova, Ricardo A / Wek, Ronald C / Lacombe, Didier / Michaud, Vincent / Musier-Forsyth, Karin

Clinical genetics

2022 Volume 103, Issue 3, Page(s) 358–363

Abstract: Aminoacyl-tRNA synthetases are enzymes that ensure accurate protein synthesis. Variants of the dual-functional cytoplasmic human glutamyl-prolyl-tRNA synthetase, EPRS1, have been associated with leukodystrophy, diabetes and bone disease. Here, we report ... ...

Abstract	Aminoacyl-tRNA synthetases are enzymes that ensure accurate protein synthesis. Variants of the dual-functional cytoplasmic human glutamyl-prolyl-tRNA synthetase, EPRS1, have been associated with leukodystrophy, diabetes and bone disease. Here, we report compound heterozygous variants in EPRS1 in a 4-year-old female patient presenting with psychomotor developmental delay, seizures and deafness. Functional studies of these two missense mutations support major defects in enzymatic function in vitro and contributed to confirmation of the diagnosis.
MeSH term(s)	Female ; Humans ; Child, Preschool ; Aminoacylation ; Amino Acyl-tRNA Synthetases/genetics ; Mutation ; Epilepsy/diagnosis ; Epilepsy/genetics ; Seizures/genetics ; Deafness/genetics
Chemical Substances	Amino Acyl-tRNA Synthetases (EC 6.1.1.-)
Language	English
Publishing date	2022-12-01
Publishing country	Denmark
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	221209-2
ISSN	1399-0004 ; 0009-9163
ISSN (online)	1399-0004
ISSN	0009-9163
DOI	10.1111/cge.14269
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Article: The Dct−/− Mouse Model to Unravel Retinogenesis Misregulation in Patients with Albinism

Tingaud-Sequeira, Angèle / Mercier, Elina / Michaud, Vincent / Pinson, Benoît / Gazova, Ivet / Gontier, Etienne / Decoeur, Fanny / McKie, Lisa / Jackson, Ian J. / Arveiler, Benoît / Javerzat, Sophie

Genes. 2022 June 27, v. 13, no. 7

2022

Abstract: We have recently identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism (OCA). Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy. Here we investigate the eye ... ...

Abstract	We have recently identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism (OCA). Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy. Here we investigate the eye phenotype in Dct⁻/⁻ mice. We show that their retinal pigmented epithelium (RPE) is severely hypopigmented from early stages, contrasting with the darker melanocytic tissues. Multimodal imaging reveals specific RPE cellular defects. Melanosomes are fewer with correct subcellular localization but disrupted melanization. RPE cell size is globally increased and heterogeneous. P-cadherin labeling of Dct⁻/⁻ newborn RPE reveals a defect in adherens junctions similar to what has been described in tyrosinase-deficient Tyrᶜ/ᶜ embryos. The first intermediate of melanin biosynthesis, dihydroxyphenylalanine (L-Dopa), which is thought to control retinogenesis, is detected in substantial yet significantly reduced amounts in Dct⁻/⁻ postnatal mouse eyecups. L-Dopa synthesis in the RPE alone remains to be evaluated during the critical period of retinogenesis. The Dct⁻/⁻ mouse should prove useful in understanding the molecular regulation of retinal development and aging of the hypopigmented eye. This may guide therapeutic strategies to prevent vision deficits in patients with albinism.
Keywords	L-dopa ; albino ; biosynthesis ; cadherins ; epithelium ; eyes ; genes ; melanin ; melanization ; mice ; neonates ; retinal degeneration ; therapeutics ; vision
Language	English
Dates of publication	2022-0627
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13071164
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A multilayered approach to the analysis of genetic data from individuals with suspected albinism.

Sergouniotis, Panagiotis I / Michaud, Vincent / Lasseaux, Eulalie / Campbell, Christopher / Plaisant, Claudio / Javerzat, Sophie / Birney, Ewan / Ramsden, Simon C / Black, Graeme C / Arveiler, Benoit

Journal of medical genetics

2023 Volume 60, Issue 12, Page(s) 1245–1249

Abstract: Albinism is a clinically and genetically heterogeneous group of conditions characterised by visual abnormalities and variable degrees of hypopigmentation. Multiple studies have demonstrated the clinical utility of genetic investigations in individuals ... ...

Abstract	Albinism is a clinically and genetically heterogeneous group of conditions characterised by visual abnormalities and variable degrees of hypopigmentation. Multiple studies have demonstrated the clinical utility of genetic investigations in individuals with suspected albinism. Despite this, the variation in the provision of genetic testing for albinism remains significant. One key issue is the lack of a standardised approach to the analysis of genomic data from affected individuals. For example, there is variation in how different clinical genetic laboratories approach genotypes that involve incompletely penetrant alleles, including the common, 'hypomorphic'
MeSH term(s)	Humans ; Albinism/genetics ; Albinism/diagnosis ; Albinism, Oculocutaneous/diagnosis ; Albinism, Oculocutaneous/genetics ; Genetic Testing ; Genotype ; Alleles
Language	English
Publishing date	2023-11-27
Publishing country	England
Document type	Journal Article
ZDB-ID	220881-7
ISSN	1468-6244 ; 0022-2593
ISSN (online)	1468-6244
ISSN	0022-2593
DOI	10.1136/jmg-2022-109088
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Article ; Online: Ophthalmologic Phenotype-Genotype Correlations in Patients With Oculocutaneous Albinism Followed in a Reference Center.

Seguy, Paul-Henri / Korobelnik, Jean-François / Delyfer, Marie-Noëlle / Michaud, Vincent / Arveiler, Benoit / Lasseaux, Eulalie / Gattoussi, Sarra / Rougier, Marie-Bénédicte / Trin, Kilian / Morice-Picard, Fanny / Ghomashchi, Nathalie / Coste, Valentine

Investigative ophthalmology & visual science

2023 Volume 64, Issue 12, Page(s) 26

Abstract: Purpose: Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ... ...

Abstract	Purpose: Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France. Methods: A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed. Results: In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A two-by-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87). Conclusions: We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA.
MeSH term(s)	Child ; Humans ; Child, Preschool ; Aged ; Ophthalmology ; Albinism, Oculocutaneous/diagnosis ; Albinism, Oculocutaneous/genetics ; Genotype ; Refractive Errors ; Phenotype
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.64.12.26
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Article ; Online: Unsuspected consequences of synonymous and missense variants in OCA2 can be detected in blood cell RNA samples of patients with albinism.

Michaud, Vincent / Sequeira, Angèle / Mercier, Elina / Lasseaux, Eulalie / Plaisant, Claudio / Hadj-Rabia, Smail / Whalen, Sandra / Bonneau, Dominique / Dieux-Coeslier, Anne / Morice-Picard, Fanny / Coursimault, Juliette / Arveiler, Benoît / Javerzat, Sophie

Pigment cell & melanoma research

2023

Abstract: Oculocutaneous albinism type 2 (OCA2) is the second most frequent form of albinism and represents about 30% of OCA worldwide. As with all types of OCA, patients present with hypopigmentation of hair and skin, as well as severe visual abnormalities. We ... ...

Abstract	Oculocutaneous albinism type 2 (OCA2) is the second most frequent form of albinism and represents about 30% of OCA worldwide. As with all types of OCA, patients present with hypopigmentation of hair and skin, as well as severe visual abnormalities. We focused on a subgroup of 29 patients for whom genetic diagnosis was pending because at least one of their identified variants in or around exon 10 of OCA2 is of uncertain significance (VUS). By minigene assay, we investigated the effect of these VUS on exon 10 skipping and showed that not only intronic but also some synonymous variants can result in enhanced exon skipping. We further found that excessive skipping of exon 10 could be detected directly on blood samples of patients and of their one parent with the causal variant, avoiding invasive skin biopsies. Moreover, we show that variants, which result in lack of detectable OCA2 mRNA can be identified from blood samples as well, as shown for the most common OCA2 pathogenic missense variant c.1327G>A/p.(Val443Ile). In conclusion, blood cell RNA analysis allows testing the potential effect of any OCA2 VUS on transcription products. This should help to elucidate yet unsolved OCA2 patients and improve genetic counseling.
Language	English
Publishing date	2023-08-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2409570-9
ISSN	1755-148X ; 1600-0749 ; 0893-5785 ; 1755-1471
ISSN (online)	1755-148X ; 1600-0749
ISSN	0893-5785 ; 1755-1471
DOI	10.1111/pcmr.13123
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Article ; Online: The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women.

Cote, Samantha / Butler, Russell / Michaud, Vincent / Lavallee, Eric / Croteau, Etienne / Mendrek, Adrianna / Lepage, Jean-Francois / Whittingstall, Kevin

Human brain mapping

2021 Volume 42, Issue 17, Page(s) 5677–5688

Abstract: Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on ...

Abstract	Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi-modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two-time points of their MC. CBF was derived from pseudo-continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = -.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MC-related hormone fluctuations in the design of functional MRI studies in this population.
MeSH term(s)	Adult ; Basilar Artery/diagnostic imaging ; Basilar Artery/physiology ; Carotid Artery, Internal/diagnostic imaging ; Carotid Artery, Internal/physiology ; Cerebrovascular Circulation/physiology ; Estrogens/blood ; Humans ; Magnetic Resonance Angiography ; Menstrual Cycle/physiology ; Neurovascular Coupling/physiology ; Progesterone/blood ; Spin Labels ; Young Adult
Chemical Substances	Estrogens ; Spin Labels ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2021-09-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.25646
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