DSpace Collection:http://sgc.anlis.gob.ar/handle/123456789/162026-04-13T17:49:02Z2026-04-13T17:49:02ZGenetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart DiseaseDelea, MarisolMassara, Lucía SEspeche, LucíaBidondo, Maria PazBarbero, PabloOliveri, JaenBrun, PalomaFabro, MónicaGalain, MicaelaFernandez, CeciliaTaboas, MelisaBruque, Carlos DavidKolomenski, EmilioIzquiedo, AgustínBerenstein, ArielCosentino, Viviana RMartinoli, CelesteVilas, MarianaRittler, MónicaMendez, RodrigoFurforo, LilianLiascovich, RosaGroisman, BorisRozental, SandraDain, Lilianahttp://sgc.anlis.gob.ar/handle/123456789/27332026-03-26T18:16:09Z2022-06-22T00:00:00ZTitle: Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease
Authors: Delea, Marisol; Massara, Lucía S; Espeche, Lucía; Bidondo, Maria Paz; Barbero, Pablo; Oliveri, Jaen; Brun, Paloma; Fabro, Mónica; Galain, Micaela; Fernandez, Cecilia; Taboas, Melisa; Bruque, Carlos David; Kolomenski, Emilio; Izquiedo, Agustín; Berenstein, Ariel; Cosentino, Viviana R; Martinoli, Celeste; Vilas, Mariana; Rittler, Mónica; Mendez, Rodrigo; Furforo, Lilian; Liascovich, Rosa; Groisman, Boris; Rozental, Sandra; Dain, Liliana
Abstract: Congenital anomalies (CA) affect 3–5% of newborns, representing the second-leading
cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of
2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a
prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian
patients with MCA and isolated CHD.We recruited 366 patients (172 with MCA and 194 with isolated
CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was
obtained from all patients, while karyotyping was performed in patients with MCA. Samples from
patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA.
Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation
sequencing (NGS). A total of 240 patients were successfully studied using at least one technique.
Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one
presented a TBX1 gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely
pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are
novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment,
we determined the genetic contribution in 27.5% of the analyzed patients.2022-06-22T00:00:00ZIsolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient PatientTaboas, MelisaFernandez, CeciliaBelli, SusanaBuzzalino, NoemíAlba, LilianaDain, Lilianahttp://sgc.anlis.gob.ar/handle/123456789/27312026-03-09T16:22:46Z2013-07-15T00:00:00ZTitle: Isolated p.H62L Mutation in the CYP21A2 Gene in a Simple Virilizing 21-Hydroxylase Deficient Patient
Authors: Taboas, Melisa; Fernandez, Cecilia; Belli, Susana; Buzzalino, Noemí; Alba, Liliana; Dain, Liliana
Abstract: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency accounts for 90%–95% of cases.This autosomal recessive disorder
has a broad spectrum of clinical forms, ranging from severe or classical, which includes the salt-wasting and simple virilizing
forms, to themild late onset or nonclassical form.Most of the disease-causingmutations described are likely to be the consequence
of nonhomologous recombination or gene conversion events between the active CYP21A2 gene and its homologous CYP21A1P
pseudogene. Nevertheless, an increasing number of naturally occurring mutations have been found. The change p.H62L is one
of the most frequent rare mutations of the CYP21A2 gene. It was suggested that the p.H62L represents a mild mutation that may
be responsible for a more severe enzymatic impairment when presented with another mild mutation on the same allele. In this
report, a 20-year-old woman carrying an isolated p.H62L mutation in compound heterozygosity with c.283-13A/C>G mutation is
described. Although amildly nonclassical phenotype was expected, clinical signs and hormonal profile of the patient are consistent
with a more severe simple virilizing form of 21-hydroxylase deficiency.The study of genotype-phenotype correlation in additional
patients would help in defining the role of p.H62L in disease manifestation.2013-07-15T00:00:00ZAn update on genetic variants of the NKX2-5Delea, MarisolSimonetti, LeandroFabbro, MónicaEspeche, LucíaTaboas, MelisaNadra, Alejandro D.Bruque, Carlos DavidDain, Lilianahttp://sgc.anlis.gob.ar/handle/123456789/27292026-03-05T17:05:46Z2020-07-01T00:00:00ZTitle: An update on genetic variants of the NKX2-5
Authors: Delea, Marisol; Simonetti, Leandro; Fabbro, Mónica; Espeche, Lucía; Taboas, Melisa; Nadra, Alejandro D.; Bruque, Carlos David; Dain, Liliana
Abstract: [ABSTRACT.] NKX2-5 is a homeodomain transcription factor that plays a crucial role in heart development. It is the first gene where a single genetic variant (GV) was found to be associated with congenital heart diseases in humans. In this study, we carried out a comprehensive survey of NKX2-5 GVs to build a unified, curated, and updated compilation of all available GVs. We retrieved a total of 1,380 unique GVs. From these, 970 had information on their frequency in the general population and 143 have been linked to pathogenic phenotypes in humans. In vitro effect was ascertained for 38 GVs. The homeodomain had the biggest cluster of pathogenic variants in the protein: 49 GVs in 60 residues, 23 in its third α-helix, where 11 missense variants may affect protein-DNA interaction or the hydrophobic core. We also pinpointed the likely location of pathogenic GVs in four linear motifs. These analyses allowed us to assign a putative explanation for the effect of 90 GVs. This study pointed to reliable pathogenicity for GVs in helix 3 of the homeodomain and may broaden the scope of functional and structural studies that can be done to better understand the effect of GVs in NKX2-5 function.
Description: Fil: Kolomenski, Jorge E. Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET; Buenos Aires, Argentina; Fil: Delea, Marisol. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Buenos Aires, Argentina; Fil: Simonetti, Leandro. Department of Chemistry-Biomedical Centre, Uppsala University; Uppsala, Sweden; Fil: Fabbro, Mónica. Laboratorio Novagen; Buenos Aires, Argentina; Fil: Espeche, Lucía D. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Buenos Aires, Argentina; Fil: Taboas, Melisa. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Buenos Aires, Argentina; Fil: Nadra, Alejandro D. Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN-CONICET; Buenos Aires, Argentina; Fil: Bruque, Carlos. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Buenos Aires, Argentina; Fil: Dain, Liliana. ANLIS Dr.C.G.Malbrán. Centro Nacional de Genética Médica; Buenos Aires, Argentina2020-07-01T00:00:00ZNovel variant in the KAT6B gene associated with Say Barber Biesecker Young SimpsonSolari, AndreaAlberto, GuillermoBenitez Medina, AnaGarcía Ayré, BrendaParisini, DanielClaps, AldanaTaboas, Melisahttp://sgc.anlis.gob.ar/handle/123456789/27282026-03-05T16:01:45Z2023-10-01T00:00:00ZTitle: Novel variant in the KAT6B gene associated with Say Barber Biesecker Young Simpson
Authors: Solari, Andrea; Alberto, Guillermo; Benitez Medina, Ana; García Ayré, Brenda; Parisini, Daniel; Claps, Aldana; Taboas, Melisa2023-10-01T00:00:00Z