@article {819, title = {Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy}, journal = {Nature Genetics}, year = {2025}, month = {Oct-04-2025}, issn = {1061-4036}, doi = {10.1038/s41588-025-02159-5}, url = {https://www.nature.com/articles/s41588-025-02159-5https://www.nature.com/articles/s41588-025-02159-5.pdfhttps://www.nature.com/articles/s41588-025-02159-5.pdfhttps://www.nature.com/articles/s41588-025-02159-5}, author = {Greene, Daniel and De Wispelaere, Koenraad and Lees, Jon and Codina-Sol{\`a}, Marta and Jensson, Brynjar O. and Hales, Emma and Katrinecz, Andrea and Nieto Molina, Esther and Sevilla Porras, Marta and Pascoal, Sonia and Valenzuela, Irene and Pfundt, Rolph and Schot, Rachel and Sleutels, Frank and Wijngaard, Robin and Arroyo Carrera, Ignacio and Duat Rodr{\'\i}guez, Anna and Atton, Giles and Casas-Alba, Didac and Donnelly, Deirdre and Fern{\'a}ndez Garoz, B{\'a}rbara and Foulds, Nicola and Garc{\'\i}a-Navas N{\'u}{\~n}ez, Deyanira and Gonz{\'a}lez Alguacil, Elena and Jarvis, Joanna and Kant, Sarina G. and Madrigal Bajo, Irene and Martinez-Monseny, Antonio F. and McKee, Shane and Sariego Jamardo, Andrea and Stefansson, Kari and Rodr{\'\i}guez-Revenga Bodi, Laia and Ortiz Cabrera, Nelmar Valentina and Sulem, Patrick and Suri, Mohnish and Van Karnebeek, Clara and Vasudevan, Pradeep and Vega Pajares, Ana Isabel and Carracedo, {\'A}ngel and Engelen, Marc and Lapunzina, Pablo and Morgan, Natasha P. and Morte, Beatriz and Rump, Patrick and Stirrups, Kathy and Tizzano, Eduardo F. and Barakat, Tahsin Stefan and O{\textquoteright}Donoghue, Michael and P{\'e}rez-Jurado, Luis Alberto and Freson, Kathleen and Mumford, Andrew D. and Turro, Ernest} } @article {665, title = {Optimised molecular genetic diagnostics of Fanconi anaemia by whole exome sequencing and functional studies.}, journal = {J Med Genet}, volume = {57}, year = {2020}, month = {2020 04}, pages = {258-268}, abstract = {

PURPOSE: Patients with Fanconi anaemia (FA), a rare DNA repair genetic disease, exhibit chromosome fragility, bone marrow failure, malformations and cancer susceptibility. FA molecular diagnosis is challenging since FA is caused by point mutations and large deletions in 22 genes following three heritability patterns. To optimise FA patients{\textquoteright} characterisation, we developed a simplified but effective methodology based on whole exome sequencing (WES) and functional studies.

METHODS: 68 patients with FA were analysed by commercial WES services. Copy number variations were evaluated by sequencing data analysis with RStudio. To test missense variants, wt FANCA cDNA was cloned and variants were introduced by site-directed mutagenesis. Vectors were then tested for their ability to complement DNA repair defects of a FANCA-KO human cell line generated by TALEN technologies.

RESULTS: We identified 93.3\% of mutated alleles including large deletions. We determined the pathogenicity of three FANCA missense variants and demonstrated that two variants reported in mutations databases as {\textquoteright}affecting functions{\textquoteright} are SNPs. Deep analysis of sequencing data revealed patients{\textquoteright} true mutations, highlighting the importance of functional analysis. In one patient, no pathogenic variant could be identified in any of the 22 known FA genes, and in seven patients, only one deleterious variant could be identified (three patients each with FANCA and FANCD2 and one patient with FANCE mutations) CONCLUSION: WES and proper bioinformatics analysis are sufficient to effectively characterise patients with FA regardless of the rarity of their complementation group, type of mutations, mosaic condition and DNA source.

}, keywords = {Cell Line, DNA Copy Number Variations, DNA Repair, DNA-Binding Proteins, Fanconi Anemia, Fanconi Anemia Complementation Group A Protein, Female, Gene Knockout Techniques, Genetic Predisposition to Disease, Humans, Male, Mutation, Missense, Polymorphism, Single Nucleotide, whole exome sequencing}, issn = {1468-6244}, doi = {10.1136/jmedgenet-2019-106249}, author = {Bogliolo, Massimo and Pujol, Roser and Aza-Carmona, Miriam and Mu{\~n}oz-Subirana, N{\'u}ria and Rodriguez-Santiago, Benjamin and Casado, Jos{\'e} Antonio and Rio, Paula and Bauser, Christopher and Reina-Castill{\'o}n, Judith and Lopez-Sanchez, Marcos and Gonzalez-Quereda, Lidia and Gallano, Pia and Catal{\'a}, Albert and Ruiz-Llobet, Ana and Badell, Isabel and Diaz-Heredia, Cristina and Hladun, Raquel and Senent, Leonort and Argiles, Bienvenida and Bergua Burgues, Juan Miguel and Ba{\~n}ez, Fatima and Arrizabalaga, Beatriz and L{\'o}pez Almaraz, Ricardo and Lopez, Monica and Figuera, {\'A}ngela and Molin{\'e}s, Antonio and P{\'e}rez de Soto, Inmaculada and Hernando, In{\'e}s and Mu{\~n}oz, Juan Antonio and Del Rosario Marin, Maria and Balma{\~n}a, Judith and Stjepanovic, Neda and Carrasco, Estela and Cuesta, Isabel and Cosuelo, Jos{\'e} Miguel and Regueiro, Alexandra and Moraleda Jimenez, Jos{\'e} and Galera-Mi{\~n}arro, Ana Maria and Rosi{\~n}ol, Laura and Carri{\'o}, Anna and Bel{\'e}ndez-Bieler, Cristina and Escudero Soto, Antonio and Cela, Elena and de la Mata, Gregorio and Fern{\'a}ndez-Delgado, Rafael and Garcia-Pardos, Maria Carmen and S{\'a}ez-Villaverde, Raquel and Barraga{\~n}o, Marta and Portugal, Raquel and Lendinez, Francisco and Hernadez, Ines and Vagace, Jos{\'e} Manue and Tapia, Maria and Nieto, Jos{\'e} and Garcia, Marta and Gonzalez, Macarena and Vicho, Cristina and Galvez, Eva and Valiente, Alberto and Antelo, Maria Luisa and Ancliff, Phil and Garc{\'\i}a, Francisco and Dopazo, Joaquin and Sevilla, Julian and Paprotka, Tobias and P{\'e}rez-Jurado, Luis Alberto and Bueren, Juan and Surralles, Jordi} }