title: Molecular testing for fragile X: analysis of 5062 tests from 1105 fragile X families--performed in 12 clinical laboratories in Spain.
abstract: Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P < 0.001). Furthermore, in mothers with intermediate alleles (45-54 repeats), there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55-59 repeats), there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.
authors.affiliation: Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, BioCruces Health Research Institute, GCV-CIBER de Enfermedades Raras (CIBERER-ISCIII), Barakaldo, 48903 Bizkaia, Spain.
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
authors.affiliation: Unidad de Genética Molecular, Centro de Bioquímica y Genética Clínica, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, 30120 Murcia, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Glover
authors.affiliation: Unidad de Genética, Hospital Universitario La Fe, 46009 Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez
authors.affiliation: Laboratorio de Genética, UDIAT-Centre Diagnòstic, Corporació Sanitària Parc Taulí, Institut Universitari UAB, Sabadell, 08208 Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Guitart
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Málaga, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Diego-Otero
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid, CSIC, 47003 Valladolid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernández-Carvajal
authors.affiliation: Consulta de Genética Clínica, Servicio de Pediatría, Hospital Clínico Universitario Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, GCV-CIBER de Enfermedades Raras (CIBERER-ISCIII), 50009 Zaragoza, Spain.
authors.forename: Feliciano J
authors.initials: FJ
authors.lastname: Ramos
authors.affiliation: Servicio de Genética, Hospital Ramón y Cajal, 28034 Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Hernández-Chico
authors.affiliation: Servicio de Biología Molecular, Hospital Virgen Macarena y Universidad de Sevilla, 41009 Sevilla, Spain.
authors.forename: Elizabet
authors.initials: E
authors.lastname: Pintado
authors.affiliation: Servicio de Genética, Hospital Universitari Son Espases, GCV-CIBER de Enfermedades Raras (CIBERER-ISCIII), Palma de Mallorca, 07010 Illes Balears, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rosell
authors.affiliation: Unidad de Genética Médica, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain.
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Calvo
authors.affiliation: Servicio de Genetica, IIS-Hospital Universitario Fundación Jiménez Díaz (IIS-FJD, UAM), CIBER de Enfermedades Raras (CIBERER-ISCIII), 28040 Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Servicio de Genética, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain.
authors.forename: María-Antonia
authors.initials: MA
authors.lastname: Ramos-Arroyo
authors.affiliation: Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, BioCruces Health Research Institute, GCV-CIBER de Enfermedades Raras (CIBERER-ISCIII), Barakaldo, 48903 Bizkaia, Spain.
authors.forename: Hiart
authors.initials: H
authors.lastname: Maortua
authors.affiliation: Servicio de Bioquímica y Genética Molecular, Hospital Clinic, IDIBAPS, CIBER de Enfermedades Raras (CIBERER-ISCIII), 08036 Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012042:Registries; D013030:Spain / Q000453:epidemiology