Albino Research Articles

Evident hypopigmentation without other ocular deficits in Dutch patients with oculocutaneous albinism type 4

To describe the phenotype of Dutch patients with oculocutaneous albinism type 4 (OCA4), 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. 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 variants in the SLC45A2 gene, c.310C > T; (p.Pro104Ser), and c.1368 + 3_1368 + 9del; (p.?). 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.

Successful rescue of a lethal Griscelli syndrome type 2 presenting with neurological involvement and hemophagocytic lymphohistiocytosis: a case report

BackgroundGriscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. It is primarily characterized by a combination of partial albinism, hemophagocytic lymphohistiocytosis (HLH) or other immunodeficiency. However, neurological involvement at onset in GS2 and treatment has rarely been described.Case presentationWe describe a 3-year-old boy with GS2 in an Asian Chinese family. He presented with progressive neurological abnormalities following unremitting fever at onset. He developed HLH during the clinical course. A novel homozygous mutation (c.1 A > G) in RAB27A gene was subsequently identified. He was then treated by HLH-1994 protocol combined with ruxolitinib and experienced a dramatic remission. He subsequently underwent a successful haploidentical hematopoietic stem cell transplantation and stayed at a good condition.ConclusionsWe reported an atypical form of GS2 manifesting as severe central nervous system involvement at onset and subsequent HLH, which was successfully rescued in time. This case also highlights the need for early consideration of immunologic and genetic evaluation for HLH in unexplained neuroinflammation in the diagnostic work up.

P360 Aggressive Inflammatory Bowel Disease is associated to Hermansky-Pudlak Syndrome: Characterization of a Puerto Rican Cohort

Abstract Background Hermansky-Pudlak Syndrome (HPS), a rare autosomal recessive disorder, is the most common single-gene disorder in Puerto Rico. It is characterized by an aberrant biogenesis of lysosome-related organelles inducing oculocutaneous albinism, bleeding diathesis, and damage to other organs. Around 30% of patients with HPS develop granulomatous enterocolitis, a Crohn’s-like inflammatory bowel disease (IBD). The mutant HPS1 gene is associated with a more severe Early Onset IBD (EO-IBD). We wish to describe a group of patients with HPS-associated IBD. Methods Puerto Ricans with HPS and concomitant IBD were recruited in our IBD clinic for a prospective cohort study. After informed consent, demographic and medical data were collected from the patient and the medical record. Variables included sex, HPS genotype, age at the time of IBD diagnosis, IBD location and behavior according to Montreal and Paris Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). Descriptive analysis was performed calculating mean and standard deviations. This study is approved by the MSC IRB. Results 13 patients with HPS and IBD, 9 with confirmed genotype 1, were identified: 8 males and 5 females. The mean age at the time of IBD diagnosis was 22 ± 11 years. 6 were diagnosed at ≤ 16 y/o (A1), 6 were diagnosed between 17-40 years (A2) and 1 patient was in the range of EO-IBD (7 y/o). 9 patients had advanced penetrating behavior (B3) of which 7 had concomitant perianal involvement. Most patients (9) had a surgical intervention; 8 have an ostomy. The majority (10) are using biologics (4 with concurrent immunomodulators). The most frequent EIM was peripheral arthropathy seen in 45%. Conclusion HPS patients had a severe course of IBD, as shown by age at diagnosis, phenotype, the prevalence of perianal disease, surgery and use of biologics. In comparison to a database of 836 Puerto Ricans with non HPS Crohn’s Disease, those with HPS were more likely to have surgeries (69% vs 55%, P=.303) and use biologics (77% vs 43%, P=.015). Gastrointestinal symptoms including bleeding may be overlooked by the primary physician. Proactive vigilance in patients with HPS to make an early diagnosis of IBD and aggressive medical treatment may result in better outcomes for these patients.

Melanosome Biogenesis in the Pigmentation of Mammalian Skin.

Melanins, the main pigments of the skin and hair in mammals, are synthesized within membrane-bound organelles of melanocytes called melanosomes. Melanosome structure and function are determined by a cohort of resident transmembrane proteins, many of which are expressed only in pigment cells and localize specifically to melanosomes. Defects in the genes that encode melanosome-specific proteins or components of the machinery required for their transport in and out of melanosomes underlie various forms of ocular or oculocutaneous albinism, characterized by hypopigmentation of the hair, skin, and eyes and by visual impairment. We review major components of melanosomes, including the enzymes that catalyze steps in melanin synthesis from tyrosine precursors, solute transporters that allow these enzymes to function, and structural proteins that underlie melanosome shape and melanin deposition. We then review the molecular mechanisms by which these components are biosynthetically delivered to newly forming melanosomes-many of which are shared by other cell types that generate cell type-specific lysosome-related organelles. We also highlight unanswered questions that need to be addressed by future investigation.

Aberrant visual population receptive fields in human albinism.

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.

The Impact of OCA2 (rs1800407) and HERC2 (rs12913832) Gene Polymorphisms on Iris Color in a Sample of Iraqi People

The study was directed in order to determine Single Nucleotide Polymorphisms (SNPs) (rs1800407 G>A)of OCA2 and (rs12913832 A>G) HERC2 genes and their association as a DNA marker with eye color in 60samples of Iraqi people. Samples were collected from College of Science / University of Baghdad and alsopeople from different areas of Baghdad, Iraq; during the two months period from September to November2020. These SNPs determination was carried out by using quantitative real-time polymerase chain reaction(qPCR) of blood samples. The results of rs12913832 genotype showed significantly differences (p<0.05) inthe green eye color group. A Survey of HERC2 gene SNP genotypes and allele frequencies in the black andgreen iris groups showed that there was a significant variation in the wild type (AA) and homozygous mutant(GG) genotype frequencies in (rs 12913832), while the SNP (rs1800407) of OCA2 concluded that gene mayhave a non-significant effect among a sample of this study comparing with green eye to black eye color.

Transformation of Long-Lived Albino Epipremnum aureum 'Golden Pothos' and Restoring Chloroplast Development.

Chloroplasts are organelles responsible for chlorophyll biosynthesis, photosynthesis, and biosynthesis of many metabolites, which are one of key targets for crop improvement. Elucidating and engineering genes involved in chloroplast development are important approaches for studying chloroplast functions as well as developing new crops. In this study, we report a long-lived albino mutant derived from a popular ornamental plant Epipremnum aureum ‘Golden Pothos’ which could be used as a model for analyzing the function of genes involved in chloroplast development and generating colorful plants. Albino mutant plants were isolated from regenerated populations of variegated ‘Golden Pothos’ whose albino phenotype was previously found to be due to impaired expression of EaZIP, encoding Mg-protoporphyrin IX monomethyl ester cyclase. Using petioles of the mutant plants as explants with a traceable sGFP gene, an efficient transformation system was developed. Expressing Arabidopsis CHL27 (a homolog of EaZIP) but not EaZIP in albino plants restored green color and chloroplast development. Interestingly, in addition to the occurrence of plants with solid green color, plants with variegated leaves and pale-yellow leaves were also obtained in the regenerated populations. Nevertheless, our study shows that these long-lived albino plants along with the established efficient transformation system could be used for creating colorful ornamental plants. This system could also potentially be used for investigating physiological processes associated with chlorophyll levels and chloroplast development as well as certain biological activities, which are difficult to achieve using green plants.

Analysis of genetic variation for a child affected with congenital insensitivity to pain with anhidrosis and albinism by whole genome sequencing

To explore the genetic variation of a Chinese family affected with congenital insensitivity to pain with anhidrosis and albinism. Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband and his parents. Whole genome sequencing (WGS) was applied when variants were not found completely. Suspected variants were validated by Sanger sequencing. WES has identified a heterozygous c.1729G>C (p.G577R) variant of NTRK1 gene and two heterozygous variants of OCA2 gene, namely c.1363A>G (p.R455G) and c.1182+1G>A. WGS has identified two additional heterozygous variants c.(851-798C>T; 851-794C>G) in deep intronic regions of the NTRK1 gene. The compound heterozygous variants of the NTRK1 gene probably underlay the congenital insensitivity to pain with anhidrosis. And the compound heterozygous variants of the OCA2 gene probably underlay the albinism in the proband. In the case where no variant is detected by WES in the coding region, WGS should be considered to screen potential variants in the whole genome.

Genetics of non-syndromic and syndromic oculocutaneous albinism in human and mouse.

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.

Effect of silver nitrate and growth regulators to enhance anther culture response in wheat (Triticum aestivum L.)

Application of chemical substances as stress pre-treatment factors may positively influence androgenetic responses in cereal and other crops. AgNO3 is an anti-ethylene compounds that played a significant role in combination with other chemicals for anther culture responses in cereal and other crop plants. For this study two local wheat cultivars viz. Kheri and Akbar were considered to evaluate the effect of AgNO3 and to optimize the suitable doses of plant growth regulators, amino acids and sucrose that supplemented in MS medium. Data were recorded on the basis of embryoids induction, regenerated green and albino plants. The results clearly stated that anther culture responses and its major outcomes on regeneration significantly increased with suitable dosages of chemicals. The most noteworthy increases embryo like structures and regenerated green plants accomplished by utilizing the combined effect of AgNO3 (50 mg/l) and as plant growth regulators IAA (1.0 mg/l) + kinetin (0.5 mg/l). Best embryo like structures (79.17%) and green plants (33.33%) were recorded in Kheri. The results clearly stated that reducing albinism and increasing embryos induction and green plants 50–75 mg/l silver nitrate along with optimum doses of IAA and kinetin showed very effective results in wheat.

Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways.

The cyclic AMP pathway promotes melanocyte differentiation by activating CREB and the cAMP-regulated transcription co-activators 1-3 (CRTC1-3). Differentiation is dysregulated in melanomas, although the contributions of CRTC proteins is unclear. We report a selective differentiation impairment in CRTC3 KO melanocytes and melanoma cells, due to downregulation of oculo-cutaneous albinism II (OCA2) and block of melanosome maturation. CRTC3 stimulates OCA2 expression by binding to CREB on a conserved enhancer, a regulatory site for pigmentation and melanoma risk. CRTC3 is uniquely activated by ERK1/2-mediated phosphorylation at Ser391 and by low levels of cAMP. Phosphorylation at Ser391 is constitutively elevated in human melanoma cells with hyperactivated ERK1/2 signaling; knockout of CRTC3 in this setting impairs anchorage-independent growth, migration, and invasiveness, whereas CRTC3 overexpression supports cell survival in response to the mitogen-activated protein kinase (MAPK) inhibitor vemurafenib. As melanomas expressing gain-of-function mutations in CRTC3 are associated with reduced survival, our results suggest that CRTC3 inhibition may provide therapeutic benefit in this setting.

Oculocutaneous Albinism Type 7 with Recurrent Infections: A Case Report

ABSTRACT Oculocutaneous albinism (OCA) is a disorder of melanin biosynthesis characterized by hypopigmentation of the skin, hair, and retinal pigment epithelium. We present the clinical and laboratory features of two siblings, born to consanguineous Turkish parents, who were diagnosed with autosomal recessive OCA type 7. We detected a homozygous mutation in the C10ORF11 gene (p.A23Rfs * 39) in both patients. Interestingly, the medical history revealed that both patients had suffered from recurrent respiratory tract infections since birth. The patients were investigated for suspected immunodeficiency and the results of the immune screening assays were normal. We believe these patients are noteworthy to report since presentation with infections has not been described in the prior descriptions of OCA type 7. As of this current writing, infectious problems have stopped in one of our cases since the age of five and a half years. Keywords: Oculocutaneous albinism type 7, recurrent infection, immune system, genetic analysis, C10ORF11 gene

La sindrome di Chediak-Higashi a esordio tardivo

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder caused by mutations in the CHS1/LYST gene, encoding for LYST protein, involved in lysosomal trafficking. It is characterized by recurrent bacterial infections, oculocutaneous albinism, silver hair, haematological and neurological alterations and a possible evolution towards the socalled accelerated phase (haemophagocytic lymphohistiocytosis). It is classified in a classic form, with infantile onset, lethal if bone marrow transplantation is not promptly performed, and in an atypical form, with adolescent/adult onset, for which a more conservative approach may be possible. The paper describes a case of hypertrophic-hyperplastic gingivopathy associated with leuko-neutropenia. The evaluation of the bone marrow smear raised the suspicion of CHS and the analysis of the clinical history highlighted the presence of suggestive criteria for atypical CHS. The genetic investigation confirmed the diagnosis.

Biophysical Compatibility of a Heterotrimeric Tyrosinase-TYRP1-TYRP2 Metalloenzyme Complex.

Tyrosinase (TYR) is a copper-containing monooxygenase central to the function of melanocytes. Alterations in its expression or activity contribute to variations in skin, hair and eye color, and underlie a variety of pathogenic pigmentary phenotypes, including several forms of oculocutaneous albinism (OCA). Many of these phenotypes are linked to individual missense mutations causing single nucleotide variants and polymorphisms (SNVs) in TYR. We previously showed that two TYR homologues, TYRP1 and TYRP2, modulate TYR activity and stabilize the TYR protein. Accordingly, to investigate whether TYR, TYRP1, and TYRP2 are biophysically compatible with various heterocomplexes, we computationally docked a high-quality 3D model of TYR to the crystal structure of TYRP1 and to a high-quality 3D model of TYRP2. Remarkably, the resulting TYR-TYRP1 heterodimer was complementary in structure and energy with the TYR-TYRP2 heterodimer, with TYRP1 and TYRP2 docking to different adjacent surfaces on TYR that apposed a third realistic protein interface between TYRP1-TYRP2. Hence, the 3D models are compatible with a heterotrimeric TYR-TYRP1-TYRP2 complex. In addition, this heterotrimeric TYR-TYRP1-TYRP2 positioned the C-terminus of each folded enzymatic domain in an ideal position to allow their C-terminal transmembrane helices to form a putative membrane embedded three-helix bundle. Finally, pathogenic TYR mutations causing OCA1A, which also destabilize TYR biochemically, cluster on an unoccupied protein interface at the periphery of the heterotrimeric complex, suggesting that this may be a docking site for OCA2, an anion channel. Pathogenic OCA2 mutations result in similar phenotypes to those produced by OCA1A TYR mutations. While this complex may be difficult to detect in vitro, due to the complex environment of the vertebrate cellular membranous system, our results support the existence of a heterotrimeric complex in melanogenesis.

Malawian mothers' experiences of raising children living with albinism: A qualitative descriptive study.

BackgroundAlbinism in humans is characterised by a reduced amount of pigment (melanin) present in the skin, hair follicles and the eye; approximately 7000–10 000 Malawians of all ages are affected. Children with these features face extreme forms of human rights abuses, even death.ObjectivesThis study aims to describe Malawian mothers’ experiences, perceptions and understanding of raising children with albinism (CWA).MethodsThe study was conducted in 2018 using a qualitative descriptive design, with purposive sampling and voluntary participation. Mothers, 18 years and older, who had given birth to a CWA and who attended the dermatology clinic of a local public hospital participated. An interview guide used during standardised, open-ended interviews was translated from English to Chichewa using forward and backward translation. Interviews were conducted in Chichewa, audio recorded, transcribed and forward and back translated from English to Chichewa. Thematic data analysis was employed.ResultsThe mean age of participants (N = 10) was 33 years; two had albinism. Emerging themes confirmed the existence of myths and stereotypes regarding albinism but from the mothers’ perspectives. Mothers reported: (1) some experiences of emotional pain, initially, but also love and acceptance of their children, despite adverse reactions of others; (2) their experiences of stigmatisation of their children and themselves, and of intended harm to their children, and (3) their own lack of knowledge and understanding of albinism.ConclusionIn our limited study, mothers’ self-reported experiences of raising CWA in Malawi highlight the need for educational programmes on albinism at national level, particularly for families with a CWA, health professionals and educators.

541 Inhibition of soluble adenylyl cyclase (sAC) rescues defective melanosomal pH and pigmentation in oculocutaneous albinism type 2 (OCA2)

Oculocutaneous albinism type 2 (OCA2) results from a defective melanosomal anion channel leading to an acidic melanosomal pH, reduced tyrosinase activity and decreased melanin production. Reduced melanin production in OCA2 affected people leads to the development of skin cancers and other forms of damage due to ultraviolet radiation. Currently, pharmacological approaches to repair melanosomal pH and pigmentation do not exist. We have shown that inhibition of soluble adenylyl cyclase (sAC) in melanocytes alkalinizes melanosomal pH and enhances tyrosinase (TYR) activity. Therefore, we asked whether inhibition of sAC would restore wild type melanosomal pH and melanin production in OCA2 melanocytes and mice. OCA2 melanocytes had a more acidic melanosomal pH and sAC inhibitors restored wild type melanosomal pH and increased tyrosinase activity. We generated Oca2-/-, sAC floxed (f/f), Tyr-CRE-ERT2 mice and induced sAC knock out via post-natal (P2-4), topical application of 4-hydroxytamoxifen. The Oca2-/-; sAC-/- mice (n=23) had noticeably darker hair color at P28 as compared to OCA2-/-; sACf/f (n=14) littermates. HPLC analysis of the hair collected on P28 showed a significant increase in total melanin in Oca2-/-; sAC-/- mice corresponding to increased amounts of both eumelanin (PTCA) and pheomelanin (AHP). Individual hair strands of Oca2-/-; sAC -/- mice revealed distinctive banding patterns as compared to Oca2-/-; sACf/f littermates, and histology showed that the Oca2-/-; sAC -/- mice also had less overall hair follicles. Thus, loss of sAC in melanocytes may affect hair morphogenesis. In conclusion, our studies show that restoring melanosomal pH by inhibiting the sAC signaling pathway is a potential therapeutic approach for the treatment of OCA2 and related diseases.

Hermansky–Pudlak syndrome: Five Chinese patients with novel variants in HPS1 and HPS6

Hermansky–Pudlak syndrome is a rare, autosomal, recessive syndromic form of albinism characterized by oculocutaneous albinism, bleeding diathesis, and a series of clinical complications. It is rarely reported in China, even with its large population base. In this study, we describe the clinical phenotypes and genotypes of five unrelated Chinese Hermansky–Pudlak syndrome pedigrees following clinical observation and next-generation sequencing. We identified three HPS-1 and two HPS-6 cases among 548 Chinese patients with oculocutaneous albinism. Five novel variants [c.1279_1280insGGAG p.(Asp427Glyfs*27) and c.875_878delACAG p.(Asp292Alafs*38) in HPS1 and c.1999C>T p.(Arg667*), c.335G>A p.(W112*), and c.1732C>T p.(R578*) in HPS6] were identified by next-generation sequencing. Our findings expand the spectrum of known variants and the genetic background of Hermansky–Pudlak syndrome, which may help in investigating phenotype–genotype relationships and aid in genetic counselling of patients with Hermansky–Pudlak syndrome.

Non-invasive prenatal detection of ocutaneous albinism type I based on cfDNA barcode-enabled single-molecule test

To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family. Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up. Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal. Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.

Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism.

Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky–Pudlak syndrome and Chédiak–Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2–186), and eight adults with a median age of 33 years (range 17–39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

Identification of a novel GPR143 mutation in a large Chinese family with isolated foveal hypoplasia

BackgroundPathogenic variants of G-protein coupled receptor 143 (GPR143) gene often leads to ocular albinism type I (OA1) characterized by nystagmus, iris and fundus hypopigmentation, and foveal hypoplasia. In this study, we identified a novel hemizygous nonsense mutation in GPR143 that caused an atypical manifestation of OA1.Case presentationWe reported a large Chinese family in which all affected individuals are afflicted with poor visual acuity and foveal hypoplasia without signs of nystagmus. Fundus examination of patients showed an absent foveal reflex and mild hypopigmentation. The fourth grade of foveal hypoplasia and the reduced area of blocked fluorescence at foveal region was detected in OCT. OCTA imaging showed the absence of foveal avascular zone. In addition, the amplitude of multifocal ERG was reduced in the central ring. Gene sequencing results revealed a novel hemizygous mutation (c.939G > A) in GPR143 gene, which triggered p.W313X. However, no iris depigmentation and nystagmus were observed among both patients and carriers.ConclusionsIn this study, we reported a novel nonsense mutation of GPR143 in a large family with poor visual acuity and isolated foveal hypoplasia without nystagmus, which further expanded the genetic mutation spectrum of GPR143.