@article {806,
	title = {Primary Ciliary Dyskinesia and Retinitis Pigmentosa: Novel  Variant and Possible Modifier Gene.},
	journal = {Cells},
	volume = {13},
	year = {2024},
	month = {2024 Mar 16},
	abstract = {<p>We report a novel  missense variant co-segregated with a familial X-linked retinitis pigmentosa (XLRP) case. The brothers were hemizygous for this variant, but only the proband presented with primary ciliary dyskinesia (PCD). Thus, we aimed to elucidate the role of the  variant and other modifier genes in the phenotypic variability observed in the family and its impact on motile cilia. The pathogenicity of the variant on the RPGR protein was evaluated by in vitro studies transiently transfecting the mutated  gene, and immunofluorescence analysis on nasal brushing samples. Whole-exome sequencing was conducted to identify potential modifier variants. In vitro studies showed that the mutated RPGR protein could not localise to the cilium and impaired cilium formation. Accordingly, RPGR was abnormally distributed in the siblings{\textquoteright} nasal brushing samples. In addition, a missense variant in  was identified. The concurrent  variant influenced ciliary mislocalisation of the protein. We provide a comprehensive characterisation of motile cilia in this XLRP family, with only the proband presenting PCD symptoms. The variant{\textquoteright}s pathogenicity was confirmed, although it alone does not explain the respiratory symptoms. Finally, the  gene may be a potential modifier for respiratory symptoms in patients with  mutations.</p>},
	keywords = {Ciliary Motility Disorders, Eye Proteins, Genes, Modifier, Humans, Male, mutation, Retinitis pigmentosa},
	issn = {2073-4409},
	doi = {10.3390/cells13060524},
	author = {Baz-Red{\'o}n, Noelia and S{\'a}nchez-Bellver, Laura and Fern{\'a}ndez-Cancio, M{\'o}nica and Rovira-Amigo, Sandra and Burgoyne, Thomas and Ranjit, Rai and Aquino, Virginia and Toro-Barrios, Noem{\'\i} and Carmona, Rosario and Polverino, Eva and Cols, Maria and Moreno-Gald{\'o}, Antonio and Camats-Tarruella, N{\'u}ria and Marfany, Gemma}
}
@article {1042,
	title = {Combined genetic and high-throughput strategies for molecular diagnosis of inherited retinal dystrophies.},
	journal = {PloS one},
	volume = {9},
	year = {2014},
	month = {2014},
	pages = {e88410},
	abstract = {Most diagnostic laboratories are confronted with the increasing demand for molecular diagnosis from patients and families and the ever-increasing genetic heterogeneity of visual disorders. Concerning Retinal Dystrophies (RD), almost 200 causative genes have been reported to date, and most families carry private mutations. We aimed to approach RD genetic diagnosis using all the available genetic information to prioritize candidates for mutational screening, and then restrict the number of cases to be analyzed by massive sequencing. We constructed and optimized a comprehensive cosegregation RD-chip based on SNP genotyping and haplotype analysis. The RD-chip allows to genotype 768 selected SNPs (closely linked to 100 RD causative genes) in a single cost-, time-effective step. Full diagnosis was attained in 17/36 Spanish pedigrees, yielding 12 new and 12 previously reported mutations in 9 RD genes. The most frequently mutated genes were USH2A and CRB1. Notably, RD3-up to now only associated to Leber Congenital Amaurosis- was identified as causative of Retinitis Pigmentosa. The main assets of the RD-chip are: i) the robustness of the genetic information that underscores the most probable candidates, ii) the invaluable clues in cases of shared haplotypes, which are indicative of a common founder effect, and iii) the detection of extended haplotypes over closely mapping genes, which substantiates cosegregation, although the assumptions in which the genetic analysis is based could exceptionally lead astray. The combination of the genetic approach with whole exome sequencing (WES) greatly increases the diagnosis efficiency, and revealed novel mutations in USH2A and GUCY2D. Overall, the RD-chip diagnosis efficiency ranges from 16\% in dominant, to 80\% in consanguineous recessive pedigrees, with an average of 47\%, well within the upper range of massive sequencing approaches, highlighting the validity of this time- and cost-effective approach whilst high-throughput methodologies become amenable for routine diagnosis in medium sized labs.},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0088410},
	url = {http://dx.plos.org/10.1371/journal.pone.0088410},
	author = {de Castro-Mir{\'o}, Marta and Pomares, Esther and Lor{\'e}s-Motta, Laura and Tonda, Raul and Joaqu{\'\i}n Dopazo and Marfany, Gemma and Gonz{\`a}lez-Duarte, Roser}
}
