Elena Mansilla
Hospital Universitario La Paz
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Publication
Featured researches published by Elena Mansilla.
Journal of Medical Genetics | 2007
Elyes Chabchoub; Laura Rodríguez; Enrique Galán; Elena Mansilla; María Luisa Martínez-Fernández; María Luisa Martínez-Frías; Jean-Pierre Fryns; Joris Vermeesch
Background: Broken chromosomes must acquire new telomeric “caps” to be structurally stable. Chromosome healing can be mediated either by telomerase through neo-telomere synthesis or by telomere capture. Aim: To unravel the mechanism(s) generating complex chromosomal mosaicisms and healing broken chromosomes. Methods: G banding, array comparative genomic hybridization (aCGH), fluorescence in-situ hybridisation (FISH) and short tandem repeat analysis (STR) was performed on a girl presenting with mental retardation, facial dysmorphism, urogenital malformations and limb anomalies carrying a complex chromosomal mosaicism. Results & discussion: The karyotype showed a de novo chromosome rearrangement with two cell lines: one cell line with a deletion 9pter and one cell line carrying an inverted duplication 9p and a non-reciprocal translocation 5pter fragment. aCGH, FISH and STR analysis enabled the deduction of the most likely sequence of events generating this complex mosaic. During embryogenesis, a double-strand break occurred on the paternal chromosome 9. Following mitotic separation of both broken sister chromatids, one acquired a telomere vianeo-telomere formation, while the other generated a dicentric chromosome which underwent breakage during anaphase, giving rise to the del inv dup(9) that was subsequently healed by chromosome 5 telomere capture. Conclusion: Broken chromosomes can coincidently be rescued by both telomere capture and neo-telomere synthesis.
Genetics and Molecular Biology | 2014
Julián Nevado; Rafaella Mergener; María Palomares-Bralo; Karen Regina Silva de Souza; Elena Vallespín; Rocío Mena; Victor Martinez-Glez; María Ángeles Mori; Fernando Santos; Sixto García-Miñaúr; Fe Amalia García-Santiago; Elena Mansilla; Luis Fernández; María Luisa de Torres; Mariluce Riegel; Pablo Lapunzina
Several new microdeletion and microduplication syndromes are emerging as disorders that have been proven to cause multisystem pathologies frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings. In this paper, we review the “new” and emergent microdeletion and microduplication syndromes that have been described and recognized in recent years with the aim of summarizing their main characteristics and chromosomal regions involved. We decided to group them by genomic region and within these groupings have classified them into those that include ID, MCA, ASD or other findings. This review does not intend to be exhaustive but is rather a quick guide to help pediatricians, clinical geneticists, cytogeneticists and/or molecular geneticists.
American Journal of Medical Genetics Part A | 2013
Elena Vallespín; Maria Palomares Bralo; M. Ángeles Mori; Rubén Martín; Sixto García-Miñaúr; Luis Fernández; M. Luisa de Torres; Fe Amalia García-Santiago; Elena Mansilla; Fernando Santos; Victoria E. M-Montaño; M. Carmen Crespo; Sol Martín; Victor Martinez-Glez; Alicia Delicado; Pablo Lapunzina; Julián Nevado
High‐resolution array comparative genomic hybridization (aCGH) is a powerful molecular cytogenetic tool that is being adopted for diagnostic evaluation of genomic imbalances and study disease mechanisms and pathogenesis. We report on the design and use, of a custom whole‐genome oligonucleotide‐based array (called KaryoArray®v3.0; Agilent‐based 8 × 60 K) for diagnostic setting, which was able to detect new and unexpected rearrangements in 11/63 (∼17.5%) of previous known pathological cases associated with known genetic disorders, and in the second step it identified at least one causal genomic imbalance responsible of the phenotype in ∼20% of patients with psychomotor development delay and/or intellectual disability. To validate the array, first; we blindly tested 120 samples; 63 genomic imbalances that had previously been detected by karyotyping, FISH and/or MLPA, and 57 sex‐matched control samples from healthy individuals; secondly a prospective study of 540 patients with intellectual disabilities, autism spectrum disorder and multiple congenital anomalies were evaluated to confirm the utility of the tool. These data indicate that implementation of array technologies as the first‐tier test may reveal that additional genomic imbalances could co‐exist in patients with trisomies and classical del/dup syndromes, suggesting that aCGH may also be indicated in these individuals, at least when phenotype does not match completely with genotype.
American Journal of Human Genetics | 2011
María Palomares; Alicia Delicado; Elena Mansilla; María Luisa de Torres; Elena Vallespín; Luis Fernández; Victor Martinez-Glez; Sixto García-Miñaúr; Julián Nevado; Fernando Santos Simarro; Victor L. Ruiz-Perez; Sally Ann Lynch; Freddie H. Sharkey; Ann-Charlotte Thuresson; Göran Annerén; E Belligni; María Luisa Martínez-Fernández; Eva Bermejo; Beata Nowakowska; Anna Kutkowska-Kazmierczak; Ewa Bocian; Ewa Obersztyn; María Luisa Martínez-Frías; Raoul C. M. Hennekam; Pablo Lapunzina
We report eight unrelated individuals with intellectual disability and overlapping submicroscopic deletions of 8q21.11 (0.66-13.55 Mb in size). The deletion was familial in one and simplex in seven individuals. The phenotype was remarkably similar and consisted of a round face with full cheeks, a high forehead, ptosis, cornea opacities, an underdeveloped alae, a short philtrum, a cupids bow of the upper lip, down-turned corners of the mouth, micrognathia, low-set and prominent ears, and mild finger and toe anomalies (camptodactyly, syndactyly, and broadening of the first rays). Intellectual disability, hypotonia, decreased balance, sensorineural hearing loss, and unusual behavior were frequently observed. A high-resolution oligonucleotide array showed different proximal and distal breakpoints in all of the individuals. Sequencing studies in three of the individuals revealed that proximal and distal breakpoints were located in unique sequences with no apparent homology. The smallest region of overlap was a 539.7 kb interval encompassing three genes: a Zinc Finger Homeobox 4 (ZFHX4), one microRNA of unknown function, and one nonfunctional pseudogen. ZFHX4 encodes a transcription factor expressed in the adult human brain, skeletal muscle, and liver. It has been suggested as a candidate gene for congenital bilateral isolated ptosis. Our results suggest that the 8q21.11 submicroscopic deletion represents a clinically recognizable entity and that a haploinsufficient gene or genes within the minimal deletion region could underlie this syndrome.
Human Mutation | 2014
Jair Tenorio; Alicia Mansilla; María Valencia; Victor Martinez-Glez; Valeria Romanelli; Pedro Arias; Nerea Castrejón; Fernando A. Poletta; Encarna Guillén-Navarro; Gema Gordo; Elena Mansilla; Fe Amalia García-Santiago; Isabel González-Casado; Elena Vallespín; María Palomares; María Ángeles Mori; Fernando Santos-Simarro; Sixto García-Miñaúr; Luis Fernández; Rocío Mena; Sara Benito-Sanz; Angela del Pozo; J.C. Silla; Kristina Ibanez; Eduardo López-Granados; Alex Martin-Trujillo; David Montaner; Karen E. Heath; Angel Campos-Barros; Joaquín Dopazo
Overgrowth syndromes (OGS) are a group of disorders in which all parameters of growth and physical development are above the mean for age and sex. We evaluated a series of 270 families from the Spanish Overgrowth Syndrome Registry with no known OGS. We identified one de novo deletion and three missense mutations in RNF125 in six patients from four families with overgrowth, macrocephaly, intellectual disability, mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjögren syndrome. RNF125 encodes an E3 ubiquitin ligase and is a novel gene of OGS. Our studies of the RNF125 pathway point to upregulation of RIG‐I‐IPS1‐MDA5 and/or disruption of the PI3K‐AKT and interferon signaling pathways as the putative final effectors.
American Journal of Medical Genetics Part A | 2015
Fe Amalia García-Santiago; Victor Martinez-Glez; Fernando Santos; Sixto García-Miñaúr; Elena Mansilla; Antonio González Meneses; Jordi Rosell; Ángeles Pérez Granero; Elena Vallespín; Luis Fernández; Blanca Sierra; María Oliver-Bonet; María Palomares; María Luisa de Torres; María Ángeles Mori; Julián Nevado; Karen E. Heath; Alicia Delicado; Pablo Lapunzina
Inverted duplication 8p associated with deletion of the short arms of chromosome 8 (invdupdel[8p]) is a relatively uncommon complex chromosomal rearrangement, with an estimated incidence of 1 in 10,000–30,000 live borns. The chromosomal rearrangement consists of a deletion of the telomeric region (8p23‐pter) and an inverted duplication of the 8p11.2–p22 region. Clinical manifestations of this disorder include severe to moderate intellectual disability and characteristic facial features. In most cases, there are also CNS associated malformations and congenital heart defects. In this work, we present the cytogenetic and molecular characterization of seven children with invdupdel(8p) rearrangements. Subsequently, we have carried out genotype–phenotype correlations in these seven patients. The majority of our patients carry a similar deletion but different size of duplications; the latter probably explaining the phenotypic variability among them. We recommend that complete clinical evaluation and detailed chromosomal microarray studies should be undertaken, enabling appropriate genetic counseling.
Clinical Dysmorphology | 2008
Laura Rodríguez; María Luisa Martínez-Fernández; Elena Mansilla; Jacobo Mendioroz; Rosa María Arteaga; Joaquín Fernández Toral; Nieves Martínez Guardia; Angel García; Fernando Centeno; Jorge Pantoja; Carmen Jovani; María Luisa Martínez-Frías
It is generally accepted that 2.5% of the patients with unexplained mental retardation and dysmorphic features have a chromosome alteration affecting the subtelomeric regions. The frequency of such alterations whether in the general population or in newborns with congenital defects, however, remains unknown. Here, we present an analysis of the subtelomeric regions in a consecutive series of 71 newborn babies with congenital defects, who displayed a normal high resolution G-band karyotype (550–850 bands). After excluding the alterations that could be considered to be polymorphisms, a total of seven subtelomeric anomalies were observed with a frequency of 9.86% (3.96–20.31). We conclude that fluorescence in-situ hybridization screening for subtelomeric alterations is relevant for infants with congenital defects detectable at birth, particularly in those newborn babies with congenital defects and a normal high resolution G-band karyotype.
American Journal of Medical Genetics Part A | 2012
Luis J. Fernández; Julián Nevado; María Luisa de Torres; Elena Mansilla; Elena Vallespín; Sixto García-Miñaúr; Rebeca Palomo; Lucía Deiros; Marta Cabrera; Elia Dina Galo; Pablo Lapunzina; Alicia Delicado
Additional Case of an Uncommon 22q11.2 Reciprocal Rearrangement in a Phenotypically Normal Mother of Children With 22q11.2 Deletion and 22q11.2 Duplication Syndromes Luis Fern andez,* Juli an Nevado, Mar ıa L. De Torres, Elena Mansilla, Elena Vallesp ın, Sixto Garc ıa-Mi~na ur, Rebeca Palomo, Luc ıa Deir os, Marta Cabrera, Elia Dina Galo, Pablo Lapunzina, and Alicia Delicado Instituto de Gen etica M edica y Molecular (INGEMM), IdiPAZ, Hospital Universitario La Paz, Universidad Aut onoma de Madrid, Madrid, Spain CIBER de Enfermedades Raras (CIBERER), ISCIII, Madrid, Spain Servicio de Cardiolog ıa Infantil, Hospital Universitario La Paz, Madrid, Spain Servicio de Neonatolog ıa, Hospital Universitario La Paz, Madrid, Spain Universidad Nacional Aut onoma de Nicaragua, Le on, Nicaragua
BMC Medical Genetics | 2014
Alicia Delicado; Luis J. Fernández; María Luisa de Torres; Julián Nevado; Fe Amalia García-Santiago; R. Rodriguez; Elena Mansilla; María Palomares; Fernando Santos-Simarro; Elena Vallespín; María Ángeles Mori; Pablo Lapunzina
BackgroundWe and others have previously reported that familial cytogenetic studies in apparently de novo genomic imbalances may reveal complex or uncommon inheritance mechanisms.MethodsA familial, combined genomic and cytogenetic approach was systematically applied to the parents of all patients with unbalanced genome copy number changes.ResultsDiscordant array-CGH and FISH results in the mother of a child with a prenatally detected 16p13.11 interstitial microduplication disclosed a balanced uncommon rearrangement in this chromosomal region. Further dosage and haplotype familial studies revealed that both the maternal grandfather and uncle had also the same 16p duplication as the proband. Genomic compensation observed in the mother probably occurred as a consequence of interchromosomal postzygotic nonallelic homologous recombination.ConclusionsWe emphasize that such a dualistic strategy is essential for the full characterization of genomic rearrangements as well as for appropriate genetic counseling.
Human Genetics | 2012
Lluís Armengol; Julián Nevado; Clara Serra-Juhé; Alberto Plaja; Carmen Mediano; Fe Amalia García-Santiago; Manel García-Aragonés; Olaya Villa; Elena Mansilla; Cristina Preciado; Luis Fernández; María Ángeles Mori; Lidia García-Pérez; Pablo Lapunzina; Luis A. Pérez-Jurado