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Results of focal macular ERGs and multifocal ERGs. Focal macular ERGs recorded from normal control (a), Case II-2 (b, c), and Case III-2 (d, e) are shown. The amplitudes of the a-wave and b-wave of Case II-2 are severely reduced. Topographic map (f–j) and local responses (k–o) of multifocal ERGs recorded from normal control (f, k), Case II-2 (g, h, l, and m), and Case III-2 (i, j, n, and o) are shown. The amplitudes of the foveal area are severely reduced in Case II-2. The results from right eyes (b, d, g, i, l, and n) and left eyes (a, c, e, f, h, j, k, m, and o) are shown. The amplitudes of the focal macular ERGs and mfERGs in proband’s daughter (III-2) were within normal limits (Figures 5(d), 5(e), 5(i), 5(j), 5(n), and 5(o)).
Source publication
The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygous RP1L1 mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectr...
Citations
... Investigators have attempted to analyze the spatial orientation and topographical changes seen in photoreceptor cells in these conditions, with genotypic correlation in a few patients. For example, reduced cone density has been described in cases with RP1L1 and KCNV2 gene variants, while in a case with the POC1B gene variant, cones sparsely distributed around the fovea, but absent in other regions, have been documented [21,25,26]. Similarly, in cone-rod dystrophy, increased cone spacing (RPGR40, CDHR143, CEP25090, and peripherin/RDS41 gene variants), sparsely observed bright cone photoreceptors in the ellipsoid zone (EZ), and enlarged photoreceptor inner segments surrounded by smaller-diameter photoreceptors (presumably rods) in areas of EZ disruption have been reported [24,[27][28][29][30][31]. ...
Inherited retinal diseases (IRDs) represent one of the major causes of progressive and irreversible vision loss in the working-age population. Over the last few decades, advances in retinal imaging have allowed for an improvement in the phenotypic characterization of this group of diseases and have facilitated phenotype-to-genotype correlation studies. As a result, the number of clinical trials targeting IRDs has steadily increased, and commensurate to this, the need for novel reproducible outcome measures and endpoints has grown. This review aims to summarize and describe the clinical presentation, characteristic imaging findings, and imaging endpoint measures that are being used in clinical research on IRDs. For the purpose of this review, IRDs have been divided into four categories: (1) panretinal pigmentary retinopathies affecting rods or cones; (2) macular dystrophies; (3) stationary conditions; (4) hereditary vitreoretinopathies.
... fluorometer (Thermo Fisher Scientific, ShahAlam, Malaysia). The DNA samples of all the index patients were investigated by whole-exome sequencing (WES) as previously described (Jaffal et al., 2019), except the sample of the index in family 13, which was analyzed using targeted NGS, as described elsewhere (Audo et al., 2012;Kikuchi et al., 2015). ...
The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C > A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G > A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G > A in USH2A, and c.3999–6A > G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2–4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.
... Since 2008, next-generation sequencing (NGS) platforms have become widely available, allowing a rapid sequencing of the HG at a reduced cost [43]. NGS technique has become a powerful tool for identifying novel genotype-RCD associations [1,15,29]. This breakthrough led to an expansion in RCD's genetic studies, which requires a comprehensive review of the research output and its trends. ...
Abstract Non-syndromic rod-cone dystrophy (RCD) is the most common condition in inherited retinal diseases. The aim of this study was to evaluate the research output and productivity related to RCD genetics per countries as classified by the human development index (HDI), by analyzing publication frequency and citations, the choice of journals and publishers, since 2000 to date. We have also analyzed the use of next-generation sequencing (NGS) in publications originating from countries with different HDIs. One thousand four hundred articles focusing on non-syndromic RCD were downloaded and analyzed. Citations and published articles were adjusted per one million individuals. The research output is significantly higher in very high HDI countries (86% of the total publications and 95% of the citations) than countries with lower HDIs in all aspects. High and medium HDI countries published together 13.6% of the total articles worldwide and received 4.6% of the citations. On the publication level, the USA (26%), United Kingdom (10%), and Japan (7%) were the top 3 among very high HDI countries, while China (6%) and India (2%) ranked first in high and medium HDI countries respectively. On the citation level, similar profiles were found. Following adjustment for population size, Switzerland (~14%), Jordan (~ 1%) and Morocco (
... Second, we have selected patients with the same genetic abnormalities because the genotype difference in the same gene may cause different courses and severities in the OMD. 6,37 However, to investigate the general mechanism of photoreceptor damage in more detail, data from a wider variety of diseases of known etiology should be examined. ...
Purpose
To analyze the microstructures of the photoreceptor layer in detail in eyes with occult macular dystrophy (OMD, Miyake's disease) by ultrahigh-resolution spectral-domain optical coherence tomography (UHR-SD-OCT).
Observations
Twenty-eight normal subjects and 5 patients with OMD of different severities were studied. Cross-sectional images through the fovea were recorded with a UHR-SD-OCT system with a depth resolution of <2.0 μm. In patients with OMD, the UHR-SD-OCT images revealed abnormal photoreceptor microstructures which were not detected in the conventional SD-OCT images. The UHR-SD-OCT images showed that the interdigitation zone (IZ) was not present and the outer segments were hyperreflective with hyperreflective dots (HRDs) aligned like string of pearls during the earlier stages. There was a disruption of the ellipsoid zone (EZ) which appeared as clusters of larger HRDs, and these HRDs became less apparent with increasing time. The outer segments became hyporeflective and rod IZ became apparent with longer duration of the disease process.
Conclusions
and Importance: The UHR-SD-OCT images show detailed characteristics of the photoreceptor microstructures of different severities during the progression of OMD. These detailed observations will help in understanding the mechanisms involved in the retinal pathology and should provide important information for their treatments.
... A majority of OMD patients are found to have missense mutation of single allele of RP1L1 gene with an autosomal dominant inheritance or sporadic presentation (1,2). Rarely, other mutations such as frame shift heterozygous or missense homozygous mutations are reported to cause OMD (6,14). Biallelic mutations of RP1L1 gene have been reported to manifest usually as autosomal recessive retinitis pigmentosa or rarely as cone-rod dystrophy. ...
... Therefore, heterozygous mutations of RP1L1 gene appear to have a milder phenotype limited to subclinical macular involvement, while homozygous mutations result in more manifest involvement of photoreceptors. Kikuchi et al. described cone dystrophy in a patient with a homozygous RP1L1 missense variant with heterozygous carriers in the family not having any phenotypic features (14). In our proband also, the phenotypic features were similarly present and associated with the homozygous RP1L1 variant and normal fundus in the heterozygous family members. ...
Background
To report the ophthalmological findings of a new phenotypical variant of RP1L1 maculopathy in an Indian patient with a homozygous variant in the RP1L1 gene
Materials and Methods
A 39-year-old male presented with complaints of disturbance in the central field of vision in both eyes (BE) for a duration of 6 months. He underwent ophthalmic examinations and diagnostic imaging. A complete retinal degeneration panel consisting of 228 genes was evaluated for pathologic variations using next-generation sequencing (NGS), which showed a variant in the RP1L1 gene.
Results
On fundus examination, he was found to have ill-defined foveal mottling in BE. Spectral domain optical coherence tomography (SD-OCT) showed sub-foveal hyper-reflective deposits and outer retinal layer disruption. A provisional diagnosis of the atypical variant of adult-onset foveomacular vitelliform dystrophy (AOFVD) was made on the basis of clinical, OCT, Fundus autofluorescence (FAF) and electrophysiological features. Genetic assessment of the proband revealed the presence of a homozygous base pair deletion in exon 4 of RP1L1 gene (chr8:g.10468194_10468195del), which results in frameshift and premature truncation of the protein 24 amino acids downstream to codon 1138 (p.Lys1138SerfsTer24). This variant was confirmed in the proband’s parents by Sanger sequencing. The diagnosis was revised to RP1L1 maculopathy, as the RP1L1 gene variant is most commonly associated with this entity.
Conclusion
This report presents the multimodal imaging of a previously unreported phenotype of RP1L1 maculopathy associated with a genetic variant of RP1L1 gene, thereby expanding the spectrum associated with RP1L1 maculopathy.
... OMD was first characterized as a hereditary macular dystrophy without apparent fundus abnormalities 5,28,29,44 (Figure 2). Patients present with normal appearing fundi despite experiencing loss of central visual field, visual acuity decline, photophobia, and color vision disturbances 5,13,19,20,23,30,32,33,40,41,46,[49][50][51]54,56 . Typically, testing reveals a normal full-field ERG, reduced multifocal (macular) ERG, normal fluorescein angiography, and photoreceptor layer thinning in the macula, associated with cone photoreceptor cell loss as observed by optical coherence tomography (OCT) and decreased foveal sensitivity detected by microperimetry 3,[16][17][18]28,29,31,32,34,44,56,60 . ...
... About 50% of patients with OMD have a detectable genetic cause, all of which have been reported to be pathogenic variants in RP1L1 4,5,7,13,17,18,21,23,50,54,61 (Table 1) (Table 1) 13,17,18,21,23 . This observation is intriguing, as this region of RP1L1 has no discernable protein domains. ...
... About 50% of patients with OMD have a detectable genetic cause, all of which have been reported to be pathogenic variants in RP1L1 4,5,7,13,17,18,21,23,50,54,61 (Table 1) (Table 1) 13,17,18,21,23 . This observation is intriguing, as this region of RP1L1 has no discernable protein domains. ...
Retinitis Pigmentosa 1-Like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important role for RP1L1 in photoreceptor biology, though its exact function is unknown. To date, RP1L1 variants have been associated with occult macular dystrophy (OMD, a cone degeneration) and retinitis pigmentosa (RP, a rod disease). Here, we summarize reported RP1L1-associated photoreceptor conditions and disease-causing RP1L1 variants. We also discuss novel associations between RP1L1 and additional photoreceptor conditions – beside OMD and RP – and fit RP1L1 into the broader scope of photoreceptor disease. RP1L1 appears to have a complex relationship with other photoreceptor proteins and may modify disease phenotype. Ultimately, further exploration of the relationship between RP1L1, other cilium components and their impact on photoreceptor health is needed.
... 12 Other phenotypes associated with RP1L1 mutations are autosomal recessive retinitis pigmentosa, autosomal recessive cone dystrophy, and possibly a digenic form of syndromic retinal dystrophy. 10,13,14 To date, numerous studies describing OMD patients with RP1L1 mutations have been reported, but limited data are available for the Chinese population. 4,15,16 Thus, this study aims to investigate the clinical and genetic characteristics of a small cohort of Chinese OMD patients. ...
Purpose:
To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort.
Methods:
Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography.
Results:
The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF.
Conclusions:
To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.
... Recently, large cohort studies have provided powerful information to determine clinical manifestations of IRD, such as fundus appearance and morphological findings, and characteristic morphological features caused by specific genes in macular dystrophy are well established [8][9][10][11][12][13][14]. For instance, typical cases with ABCA4 retinopathy show disruption of photoreceptor layers with thinned sensory retina at the macula, and cases with RP1L1 retinopathy demonstrate blurring of photoreceptor ellipsoid zone (EZ) and loss of photoreceptor interdigitation zone (IZ) [8,11,[15][16][17][18][19][20][21][22]. ...
Purpose:
To illustrate a data-driven deep learning approach to predicting the gene responsible for the inherited retinal disorder (IRD) in macular dystrophy caused by ABCA4 and RP1L1 gene aberration in comparison with retinitis pigmentosa caused by EYS gene aberration and normal subjects.
Methods:
Seventy-five subjects with IRD or no ocular diseases have been ascertained from the database of Japan Eye Genetics Consortium; 10 ABCA4 retinopathy, 20 RP1L1 retinopathy, 28 EYS retinopathy, and 17 normal patients/subjects. Horizontal/vertical cross-sectional scans of optical coherence tomography (SD-OCT) at the central fovea were cropped/adjusted to a resolution of 400 pixels/inch with a size of 750 × 500 pix2 for learning. Subjects were randomly split following a 3 : 1 ratio into training and test sets. The commercially available learning tool, Medic mind was applied to this four-class classification program. The classification accuracy, sensitivity, and specificity were calculated during the learning process. This process was repeated four times with random assignment to training and test sets to control for selection bias. For each training/testing process, the classification accuracy was calculated per gene category.
Results:
A total of 178 images from 75 subjects were included in this study. The mean training accuracy was 98.5%, ranging from 90.6 to 100.0. The mean overall test accuracy was 90.9% (82.0-97.6). The mean test accuracy per gene category was 100% for ABCA4, 78.0% for RP1L1, 89.8% for EYS, and 93.4% for Normal. Test accuracy of RP1L1 and EYS was not high relative to the training accuracy which suggests overfitting.
Conclusion:
This study highlighted a novel application of deep neural networks in the prediction of the causative gene in IRD retinopathies from SD-OCT, with a high prediction accuracy. It is anticipated that deep neural networks will be integrated into general screening to support clinical/genetic diagnosis, as well as enrich the clinical education.
... 10 In addition, other phenotypes associated with RP1L1 variants have been reported: autosomal recessive retinitis pigmentosa associated with biallelic deleterious RP1L1 variants, mild generalized cone dysfunction by biallelic missense RP1L1 variants, and syndromic retinitis pigmentosa caused by digenic disorders. 7,[16][17][18][19] Characteristic microstructural changes of the photoreceptors are helpful in making a clinical diagnosis of OMD. 4,9,13,15,[19][20][21][22][23] The blurring of the ellipsoid zone (EZ) and absence of the interdigitation zone (IZ) of photoreceptors at the macula demonstrated by spectral-domain OCT are specific in autosomal dominant OMD families harboring a heterozygous pathogenic RP1L1 variant. ...
Purpose:
To describe the clinical and genetic characteristics of the cohort enrolled in the East Asian studies of occult macular dystrophy (OMD).
Design:
International, multicenter, retrospective cohort studies.
Participants:
A total of 36 participants from 21 families with a clinical diagnosis of OMD and harboring pathogenic RP1L1 variants (i.e., Miyake disease) were enrolled from 3 centers in Japan, China, and South Korea.
Methods:
A detailed history was obtained, and comprehensive ophthalmological examinations including spectral-domain OCT were performed. All detected sequence variants in the RP1L1 gene were reviewed, and in silico analysis was performed, including allele frequency analyses and pathogenicity predictions.
Main outcome measures:
Onset of disease, visual acuity (VA) converted to the logarithm of the minimum angle of resolution (logMAR), OCT findings, and effect of detected variants.
Results:
Eleven families from Japan, 6 from South Korea, and 4 from China were recruited. There were 12 female and 24 male participants. The median age of onset was 25.5 years (range, 2-73), and the median age at the latest examination was 46.0 years (range, 11-86). The median VA (logMAR) was 0.65 (range, -0.08-1.22) in the right eye and 0.65 (-0.08-1.10) in the left eye. A significant correlation between onset of disease and VA was revealed. The Classical morphologic phenotype showing both blurred ellipsoid zone and absence of interdigitation zone of the photoreceptors was demonstrated in 30 patients (83.3%), and subtle photoreceptor architectural changes were demonstrated in 6 patients (16.6%). Eight pathogenic RP1L1 variants were identified, including 6 reported variants and 1 novel variant: p.R45W, p.T1194M/p.T1196I (complex), p.S1199C, p.G1200A, p.G1200D, p.V1201G, and p.S1198F, respectively. Two variants were recurrent: p.R45W (11 families, 52.4%) and p.S1199C (5 families, 23.8%). The pathogenic missense variants in 10 families (47.6%) were located within the previously reported unique motif, including 6 amino acids (1196-1201).
Conclusions:
There is a large spectrum of clinical findings in Miyake disease, including various onset of disease and VA, whereas the characteristic photoreceptor microstructures were shared in most cases. Two hot spots including amino acid numbers 45 and 1196-1201 in the RP1L1 gene were confirmed in the East Asian population.
... Interestingly, mutations in RPGRIP1L and RPGRIP1 result in different mouse and human ciliopathies (Tables S1, S2 and S3). RPGRIP1 mutations lead to eye defects in mice and humans (Abouzeid et al., 2016;Booij et al., 2005;Chen et al., 2013;Coppieters et al., 2014;Dryja et al., 2001;Fakhratova, 2013;Fernández-Martínez et al., 2011;Galvin et al., 2005;Gerber et al., 2001;Hameed et al., 2003;Han et al., 2017;Hanein et al., 2004;Huang et al., 2017Huang et al., , 2016Huang et al., , 2013Imani et al., 2018;Kikuchi et al., 2015;Li et al., 2011Li et al., , 2009McKibbin et al., 2010;Neveling et al., 2013;Roepman et al., 2005;Sanchez-Navarro et al., 2018;Saqib et al., 2015;Seong et al., 2008;Suzuki et al., 2014;Tiwari et al., 2016;Vallespin et al., 2007;Verma et al., 2013;Walia et al., 2010;Wang et al., 2016Wang et al., , 2013Won et al., 2009;Zernant et al., 2005;Zhao et al., 2003), RPGRIP1L mutations affect the development of the brain, the eyes, the lung, the heart, the kidneys, the liver, the limbs, and the skin (Alazami et al., 2012;Arts et al., 2007;Besse et al., 2011;Brancati et al., 2008;Chen et al., 2015;Delous et al., 2007;Doherty et al., 2010;Fahim et al., 2011;Gerhardt et al., 2013;Halbritter et al., 2012;Khanna et al., 2009;Laclef et al., 2015;Otto et al., 2011;Stratigopoulos et al., 2014;Summers et al., 2017;Szymanska et al., 2012;Vierkotten et al., 2007;Wolf et al., 2007). Patients bearing mutations in RPGRIP1 suffer from Retinitis Pigmentosa (RP), Cone Rod Dystrophy (CRD), Inherited Retinal Dystrophy (IRD) and Leber's Congenital Amaurosis (LCA) (Abouzeid et al., 2016;Booij et al., 2005;Chen et al., 2013;Coppieters et al., 2014;Dryja et al., 2001;Fakhratova, 2013;Fernández-Martínez et al., 2011;Galvin et al., 2005;Gerber et al., 2001;Hameed et al., 2003;Han et al., 2017;Hanein et al., 2004;Huang et al., 2017Huang et al., , 2016Huang et al., , 2013Imani et al., 2018;Kikuchi et al., 2015;Li et al., 2011Li et al., , 2009McKibbin et al., 2010;Neveling et al., 2013;Roepman et al., 2005;Sanchez-Navarro et al., 2018;Saqib et al., 2015;Seong et al., 2008;Suzuki et al., 2014;Tiwari et al., 2016;Vallespin et al., 2007;Verma et al., 2013;Walia et al., 2010;Wang et al., 2016Wang et al., , 2013Zernant et al., 2005), while patients with mutations in RPGRIP1L suffer from Meckel syndrome (MKS), Joubert syndrome (JBTS), Cerebellar Vermis Aplasia Oligophrenia Congenital Ataxia Coloboma Hepatic Fibrosis (COACH), Nephronophtisis (NPHP), Bardet-Biedl syndrome (BBS), Retinitis Pigmentosa (RP) and Leber's Congenital Amaurosis (LCA) (Alazami et al., 2012;Arts et al., 2007;Brancati et al., 2008;Chaki et al., 2011;Delous et al., 2007;Doherty et al., 2010;Fahim et al., 2011;Halbritter et al., 2012;Khanna et al., 2009;Otto et al., 2011;Summers et al., 2017;Szymanska et al., 2012;Wolf et al., 2007). ...
... RPGRIP1 mutations lead to eye defects in mice and humans (Abouzeid et al., 2016;Booij et al., 2005;Chen et al., 2013;Coppieters et al., 2014;Dryja et al., 2001;Fakhratova, 2013;Fernández-Martínez et al., 2011;Galvin et al., 2005;Gerber et al., 2001;Hameed et al., 2003;Han et al., 2017;Hanein et al., 2004;Huang et al., 2017Huang et al., , 2016Huang et al., , 2013Imani et al., 2018;Kikuchi et al., 2015;Li et al., 2011Li et al., , 2009McKibbin et al., 2010;Neveling et al., 2013;Roepman et al., 2005;Sanchez-Navarro et al., 2018;Saqib et al., 2015;Seong et al., 2008;Suzuki et al., 2014;Tiwari et al., 2016;Vallespin et al., 2007;Verma et al., 2013;Walia et al., 2010;Wang et al., 2016Wang et al., , 2013Won et al., 2009;Zernant et al., 2005;Zhao et al., 2003), RPGRIP1L mutations affect the development of the brain, the eyes, the lung, the heart, the kidneys, the liver, the limbs, and the skin (Alazami et al., 2012;Arts et al., 2007;Besse et al., 2011;Brancati et al., 2008;Chen et al., 2015;Delous et al., 2007;Doherty et al., 2010;Fahim et al., 2011;Gerhardt et al., 2013;Halbritter et al., 2012;Khanna et al., 2009;Laclef et al., 2015;Otto et al., 2011;Stratigopoulos et al., 2014;Summers et al., 2017;Szymanska et al., 2012;Vierkotten et al., 2007;Wolf et al., 2007). Patients bearing mutations in RPGRIP1 suffer from Retinitis Pigmentosa (RP), Cone Rod Dystrophy (CRD), Inherited Retinal Dystrophy (IRD) and Leber's Congenital Amaurosis (LCA) (Abouzeid et al., 2016;Booij et al., 2005;Chen et al., 2013;Coppieters et al., 2014;Dryja et al., 2001;Fakhratova, 2013;Fernández-Martínez et al., 2011;Galvin et al., 2005;Gerber et al., 2001;Hameed et al., 2003;Han et al., 2017;Hanein et al., 2004;Huang et al., 2017Huang et al., , 2016Huang et al., , 2013Imani et al., 2018;Kikuchi et al., 2015;Li et al., 2011Li et al., , 2009McKibbin et al., 2010;Neveling et al., 2013;Roepman et al., 2005;Sanchez-Navarro et al., 2018;Saqib et al., 2015;Seong et al., 2008;Suzuki et al., 2014;Tiwari et al., 2016;Vallespin et al., 2007;Verma et al., 2013;Walia et al., 2010;Wang et al., 2016Wang et al., , 2013Zernant et al., 2005), while patients with mutations in RPGRIP1L suffer from Meckel syndrome (MKS), Joubert syndrome (JBTS), Cerebellar Vermis Aplasia Oligophrenia Congenital Ataxia Coloboma Hepatic Fibrosis (COACH), Nephronophtisis (NPHP), Bardet-Biedl syndrome (BBS), Retinitis Pigmentosa (RP) and Leber's Congenital Amaurosis (LCA) (Alazami et al., 2012;Arts et al., 2007;Brancati et al., 2008;Chaki et al., 2011;Delous et al., 2007;Doherty et al., 2010;Fahim et al., 2011;Halbritter et al., 2012;Khanna et al., 2009;Otto et al., 2011;Summers et al., 2017;Szymanska et al., 2012;Wolf et al., 2007). Recently, we reported that Rpgrip1l and Rpgrip1 regulate TZ assembly synergistically . ...
RPGRIP1L is an evolutionary highly conserved gene encoding a protein that localises at the transition zone of primary cilia. Mutations in RPGRIP1L result in ciliopathies, severe human diseases caused by dysfunctional cilia. Patients with mutations in this gene often suffer from an impaired development of not only one but various organs. To elucidate the function of Rpgrip1l in human development and the mechanisms underlying ciliopathies, different model organisms are used. In this review article, we summarise the findings of these investigations comprising novel functions of Rpgrip1l and the most promising therapeutic approaches.
