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1. Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina

Author

Schlottmann, Patricio G., Luna, José D., Labat, Natalia, Yadarola, María Belén, Bainttein, Silvina, Esposito, Evangelina, Ibañez, Agustina, Barbaro, Evangelina Ivón, Álvarez Mendiara, Alejandro, Picotti, Carolina P., Chirino Misisian, Andrea, Andreussi, Luciana, Gras, Julieta, Capalbo, Luciana, Visotto, Mauro, Dipierri, José E., Alcoba, Emilio, Fernández Gabrielli, Laura, Ávila, Silvia, Aucar, María Emilia, Martin, Daniel M., Ormaechea, Gerardo Juan, Inga, M. Eugenia, Francone, Aníbal A., Charles, Martin, Zompa, Tamara, Pérez, Pablo Javier, Lotersztein, Vanesa, Nuova, Pedro J., Canonero, Ivana B., Mahroo, Omar A., Michaelides, Michel, Arno, Gavin, and Daich Varela, Malena

Published
2023
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2. Identification of copy‐number variants in patients with overgrowth disorders.

Author

Parra, Alejandro, Tenorio‐Castano, Jair, Nevado, Julián, Cazalla, Mario, Miranda‐Alcaraz, Lucía, Gallego‐Zazo, Natalia, Silván, Cristina, Arias, Pedro, Pozo‐Román, Jesús, Ballesta‐Martínez, María Juliana, Guillén‐Navarro, Encarna, Arroyo, Ignacio, Lotersztein, Vanesa, Cosentino, Viviana, González‐Meneses, Antonio, Galán, Enrique, Rosell, Jordi, Ramos, Feliciano, Plasencia, Antonio, and Rosa, Alberto L.

Subjects
WHOLE genome sequencing, SCIENTIFIC literature, STANDARD deviations, RELATIVES, GENDER
Abstract

Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2–3 standard deviations above the mean for age, gender, and ethnic group. Several copy‐number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1‐qter, among many others. In this study, we have applied 850K SNP‐arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well‐established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome.

Author

Buonfiglio, Paula Inés, Izquierdo, Agustín, Pace, Mariela Vanina, Grinberg, Sofia, Lotersztein, Vanesa, Brun, Paloma, Bruque, Carlos David, Elgoyhen, Ana Belén, and Dalamón, Viviana

Subjects
SINGLE nucleotide polymorphisms, DNA copy number variations, GENETIC testing, GENETIC disorder diagnosis, GENETIC counseling
Abstract

Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina

Author

Schlottmann, Patricio, primary, Pinto, José Luna, additional, Labat, Natalia, additional, Yadarola, Maria Belen, additional, Bainttein, Silvina, additional, Esposito, Evangelina, additional, Ibañez, Agustina, additional, Barbaro, Evangelina, additional, Mendiara, Alejandro Álvarez, additional, Picotti, Carolina, additional, Misisian, Andrea Chirino, additional, Andreussi, Luciana, additional, Gras, Julieta, additional, Capalbo, Luciana, additional, Visotto, Mauro, additional, Dipierri, José, additional, Alcoba, Emilio, additional, Gabrielli, Laura Fernández, additional, Ávila, Silvia, additional, Aucar, Maria Emilia, additional, Martin, Daniel, additional, Ormaechea, Gerardo, additional, Inga, M., additional, Francone, Anibal, additional, Charles, Martin, additional, Zompa, Tamara, additional, Pérez, Pablo, additional, Lotersztein, Vanesa, additional, Nuova, Pedro, additional, Canonero, Ivana, additional, Michaelides, Michel, additional, Arno, Gavin, additional, and Varela, Malena Daich, additional

Published
2022
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10. Additional file 3 of Inflammatory cutaneous lesions and pulmonary manifestations in a new patient with autosomal recessive ISG15 deficiency case report

Author

Buda, Guadalupe, Valdez, Rita María, Biagioli, German, Olivieri, Federico A., Affranchino, Nicolás, Bouso, Carolina, Lotersztein, Vanesa, Dusan Bogunovic, Bustamante, Jacinta, and Martí, Marcelo A.

Abstract

Additional file 3: Table S3. Immune evaluation results. *25th and 75th percentiles of age-related normal values for lymphocyte subpopulations. Cellular immunology laboratory of “Pediatric Hospital Prof. Dr. Juan P. Garrahan”. + Reference values for serum IgA, IgG and IgM according to age, expressed as median ± SD. Ref: Stiehm ER, Fudenberg HH. Serum levels of Immune Globulins in health and disease. Pediatrics 37: 715, 1966.

Published
2020
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11. Additional file 1 of Inflammatory cutaneous lesions and pulmonary manifestations in a new patient with autosomal recessive ISG15 deficiency case report

Author

Buda, Guadalupe, Valdez, Rita María, Biagioli, German, Olivieri, Federico A., Affranchino, Nicolás, Bouso, Carolina, Lotersztein, Vanesa, Dusan Bogunovic, Bustamante, Jacinta, and Martí, Marcelo A.

Abstract

Additional file 1: Table S1. Primary genetic panel studied. Genes related to monogenic autoinflammatory diseases.

Published
2020
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12. Additional file 2 of Inflammatory cutaneous lesions and pulmonary manifestations in a new patient with autosomal recessive ISG15 deficiency case report

Author

Buda, Guadalupe, Valdez, Rita María, Biagioli, German, Olivieri, Federico A., Affranchino, Nicolás, Bouso, Carolina, Lotersztein, Vanesa, Dusan Bogunovic, Bustamante, Jacinta, and Martí, Marcelo A.

Abstract

Additional file 2: Table S2. Patients reported to date with ISG15 deficiency, including ours. IBGC refers to idiopathic basal ganglia calcification.

Published
2020
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15. GJB2 and GJB6 genes: Molecular study and identification of novel GJB2 mutations in the hearing-impaired argentinean population

Author

Dalamon, Viviana Karina, Lotersztein, Vanesa, Béhèran, Agustina, Lipovsek, Maria Marcela, Diamante, Fernando, Pallares, Norma, Francipane, Liliana, Frechtel, Gustavo Daniel, Paoli, Bibiana, Mansilla, Enrique, Diamante, Vicente, and Elgoyhen, Ana Belen

Subjects
CONNEXIN 30, CIENCIAS MÉDICAS Y DE LA SALUD, GJB6, CONNEXIN 26, MUTATION, NOVEL, Medicina Critica y de Emergencia, Medicina Clínica, DEAFNESS, GJB2
Abstract

Mutations in the GJB2 gene are responsible for more than half of all cases of recessive non-syndromic deafness. This article presents a mutation analysis of the GJB2, GJB6, OTOF and MTRNR1 genes in 252 patients with sensorineural non-syndromic hearing loss. Thirty-one different mutations were identified in GJB2 and GJB6 in 86 of the 252 (34%) patients. We describe for the first time two new mutations in GJB2: the missense mutation c.29 T>C (p.Leu10Pro) in the N terminal domain and c.326 G>T (p.Gly109Val) in the intracytoplasmic domain of connexin 26. This work shows the high prevalence of GJB2 mutations in the Argentinean population, with frequencies that are comparable to those of the Mediterranean area. Most important, it adds two novel GJB2 mutations to be taken into consideration in the genetic diagnosis of non-syndromic sensorineural hearing loss. Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Lotersztein, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Béhèran, Agustina. Centro de Implantes Cocleares "Prof. Dr. Vicente Diamante"; Argentina Fil: Lipovsek, Maria Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Diamante, Fernando. Centro de Implantes Cocleares "Prof. Dr. Vicente Diamante"; Argentina Fil: Pallares, Norma. Centro de Implantes Cocleares "Prof. Dr. Vicente Diamante"; Argentina Fil: Francipane, Liliana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Paoli, Bibiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Mansilla, Enrique. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Diamante, Vicente. Centro de Implantes Cocleares "Prof. Dr. Vicente Diamante"; Argentina Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina

Published
2010

17. Connexin 26 (GJB2) mutation in an Argentinean patient with keratitisichthyosis-deafness (KID) syndrome: a case report.

Author

Dalamón, Viviana Karina, Buonfiglio, Paula, Larralde, Margarita, Craig, Patricio, Lotersztein, Vanesa, Choate, Keith, Pallares, Norma, Diamante, Vicente, and Elgoyhen, Ana Belén

Subjects
CONNEXIN genetics
Abstract

Background: Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare condition characterized by pre-lingual sensorineural deafness with skin hyperkeratinization. The primary cause of the disease is a loss-of-function mutation in the GJB2 gene. Mutations in Argentinean patients have not been described. Case presentation: We studied a 2 year-old boy with bilateral congenital sensorineural deafness with dry skin over the entire body, hypotrichosis of the scalp, thin and light-blond hair. Analysis of the GJB2 gene nucleotide sequence revealed the substitution of guanine-148 by adenine predicted to result in an Asp50Asn amino acid substitution. Conclusion: This is the first KID report in a patient from Argentina. This de novo mutation proved to be the cause of keratitis-ichthyosis-deafness syndrome (KID-syndrome) in the patient, and has implications in medical genetic practice. [ABSTRACT FROM AUTHOR]

Published
2016
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20. Snijders Blok–Campeau Syndrome: Description of 20 Additional Individuals with Variants in CHD3 and Literature Review.

Author

Pascual, Patricia, Tenorio-Castano, Jair, Mignot, Cyril, Afenjar, Alexandra, Arias, Pedro, Gallego-Zazo, Natalia, Parra, Alejandro, Miranda, Lucia, Cazalla, Mario, Silván, Cristina, Heron, Delphine, Keren, Boris, Popa, Ioana, Palomares, María, Rikeros, Emi, Ramos, Feliciano J., Almoguera, Berta, Ayuso, Carmen, Swafiri, Saoud Tahsin, and Barbero, Ana Isabel Sánchez

Subjects
LITERATURE reviews, DNA-binding proteins, DNA helicases, AUTISM spectrum disorders, DEVELOPMENTAL delay
Abstract

Snijders Blok–Campeau syndrome (SNIBCPS, OMIM# 618205) is an extremely infrequent disease with only approximately 60 cases reported so far. SNIBCPS belongs to the group of neurodevelopmental disorders (NDDs). Clinical features of patients with SNIBCPS include global developmental delay, intellectual disability, speech and language difficulties and behavioral disorders like autism spectrum disorder. In addition, patients with SNIBCPS exhibit typical dysmorphic features including macrocephaly, hypertelorism, sparse eyebrows, broad forehead, prominent nose and pointed chin. The severity of the neurological effects as well as the presence of other features is variable among subjects. SNIBCPS is caused likely by pathogenic and pathogenic variants in CHD3 (Chromodomain Helicase DNA Binding Protein 3), which seems to be involved in chromatin remodeling by deacetylating histones. Here, we report 20 additional patients with clinical features compatible with SNIBCPS from 17 unrelated families with confirmed likely pathogenic/pathogenic variants in CHD3. Patients were analyzed by whole exome sequencing and segregation studies were performed by Sanger sequencing. Patients in this study showed different pathogenic variants affecting several functional domains of the protein. Additionally, none of the variants described here were reported in control population databases, and most computational predictors suggest that they are deleterious. The most common clinical features of the whole cohort of patients are global developmental delay (98%) and speech disorder/delay (92%). Other frequent features (51–74%) include intellectual disability, hypotonia, hypertelorism, abnormality of vision, macrocephaly and prominent forehead, among others. This study expands the number of individuals with confirmed SNIBCPS due to pathogenic or likely pathogenic variants in CHD3. Furthermore, we add evidence of the importance of the application of massive parallel sequencing for NDD patients for whom the clinical diagnosis might be challenging and where deep phenotyping is extremely useful to accurately manage and follow up the patients. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Clinical Heterogeneity and Different Phenotypes in Patients with SETD2 Variants: 18 New Patients and Review of the Literature.

Author

Parra, Alejandro, Rabin, Rachel, Pappas, John, Pascual, Patricia, Cazalla, Mario, Arias, Pedro, Gallego-Zazo, Natalia, Santana, Alfredo, Arroyo, Ignacio, Artigas, Mercè, Pachajoa, Harry, Alanay, Yasemin, Akgun-Dogan, Ozlem, Ruaud, Lyse, Couque, Nathalie, Levy, Jonathan, Porras-Hurtado, Gloria Liliana, Santos-Simarro, Fernando, Ballesta-Martinez, Maria Juliana, and Guillén-Navarro, Encarna

Subjects
LITERATURE reviews, AUTISM spectrum disorders, SCIENTIFIC literature, PHENOTYPES, MISSENSE mutation
Abstract

SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan–Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin–Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants.

Author

Cardoso, Leila Cabral de Almeida, Parra, Alejandro, Gil, Cristina Ríos, Arias, Pedro, Gallego, Natalia, Romanelli, Valeria, Kantaputra, Piranit Nik, Lima, Leonardo, Llerena Júnior, Juan Clinton, Arberas, Claudia, Guillén-Navarro, Encarna, Nevado, Julián, Tenorio-Castano, Jair, and Lapunzina, Pablo

Subjects
PROTEIN metabolism, SEQUENCE analysis, GENETIC mutation, RISK assessment, BECKWITH-Wiedemann syndrome, CHROMOSOME abnormalities, GENES, RESEARCH funding, EPIGENOMICS
Abstract

Simple Summary: Beckwith–Wiedemann syndrome (BWS) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. BWS is considered a spectrum disorder (BWSp) with an increased neoplasm incidence. CDKN1C variants have been reported in 5–10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing. We present 21 cases, 19 of which were classified as classical BWS and 1 that developed a mediastinal ganglioneuroma. Our study supports the high heterogeneity of the clinical features of BWSp and adds evidence on tumour development in this BWSp molecular subgroup. Genotype–phenotype correlation studies of patients with suspected BWS are essential for improving the diagnosis and assessing whether its cause can be directly related to the BWS clinical spectrum in the few cases that develop tumours. Beckwith–Wiedemann syndrome spectrum (BWSp) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. Clinical features include overgrowth, macroglossia, neonatal hypoglycaemia, omphalocele, hemihyperplasia, cleft palate, and increased neoplasm incidence. The most common molecular defect observed is hypomethylation at the imprinting centre 2 (KCNQ1OT1:TSS DMR) in the maternal allele, which accounts for approximately 60% of cases, although CDKN1C pathogenic variants have been reported in 5–10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with pathogenic or likely pathogenic CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing, with special focus on the neoplasm incidence, given that there is scarce knowledge of this feature in CDKN1C-associated BWSp. In total, we evaluated 21 cases of BWSp with CDKN1C variants; 19 were classified as classical BWS according to the BWSp scoring classification by Brioude et al. One of our patients developed a mediastinal ganglioneuroma. Our study adds evidence that tumour development in patients with BWSp and CDKN1C variants is infrequent, but it is extremely relevant to the patient's follow-up and supports the high heterogeneity of BWSp clinical features associated with CDKN1C variants. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Clinical and molecular analyses of Beckwith-Wiedemann syndrome: Comparison between spontaneous conception and assisted reproduction techniques.

Author

Tenorio, Jair, Romanelli, Valeria, Martin‐Trujillo, Alex, Fernández, García‐Moya, Segovia, Mabel, Perandones, Claudia, Pérez Jurado, Luis A., Esteller, Manel, Fraga, Mario, Arias, Pedro, Gordo, Gema, Dapía, Irene, Mena, Rocío, Palomares, María, Pérez de Nanclares, Guiomar, Nevado, Julián, García‐Miñaur, Sixto, Santos‐Simarro, Fernando, Martinez‐Glez, Víctor, and Vallespín, Elena

Abstract

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by an excessive prenatal and postnatal growth, macrosomia, macroglossia, and hemihyperplasia. The molecular basis of this syndrome is complex and heterogeneous, involving genes located at 11p15.5. BWS is correlated with assisted reproductive techniques. BWS in individuals born following assisted reproductive techniques has been found to occur four to nine times higher compared to children with to BWS born after spontaneous conception. Here, we report a series of 187 patients with to BWS born either after assisted reproductive techniques or conceived naturally. Eighty-eight percent of BWS patients born via assisted reproductive techniques had hypomethylation of KCNQ1OT1:TSS-DMR in comparison with 49% for patients with BWS conceived naturally. None of the patients with BWS born via assisted reproductive techniques had hypermethylation of H19/IGF2:IG-DMR, neither CDKN1 C mutations nor patUPD11. We did not find differences in the frequency of multi-locus imprinting disturbances between groups. Patients with BWS born via assisted reproductive techniques had an increased frequency of advanced bone age, congenital heart disease, and decreased frequency of earlobe anomalies but these differences may be explained by the different molecular background compared to those with BWS and spontaneous fertilization. We conclude there is a correlation of the molecular etiology of BWS with the type of conception. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2016
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24. GJB2 and GJB6 Genetic Variant Curation in an Argentinean Non-Syndromic Hearing-Impaired Cohort

Author

Viviana Karina Dalamon, Leonela Natalia Luce, Sebastián Menazzi, Ana Belén Elgoyhen, Vanesa Lotersztein, Bibiana Paoli, Paula Inés Buonfiglio, Florencia Giliberto, and Carlos David Bruque

Subjects
0301 basic medicine, medicine.medical_specialty, lcsh:QH426-470, CURATION, Hearing loss, Genetic counseling, Genomics, Bioinformatics, Article, purl.org/becyt/ford/1 [https], HEARING LOSS, 03 medical and health sciences, 0302 clinical medicine, GJB6, Genetics, otorhinolaryngologic diseases, Medicine, argentina, GENETIC VARIANTS, purl.org/becyt/ford/1.6 [https], Genetics (clinical), hearing loss, ARGENTINA, biology, Molecular pathology, business.industry, genetic variants, curation, GJB2, lcsh:Genetics, 030104 developmental biology, Categorization, Cohort, biology.protein, Medical genetics, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Genetic variants in GJB2 and GJB6 genes are the most frequent causes of hereditary hearing loss among several deaf populations worldwide. Molecular diagnosis enables proper genetic counseling and medical prognosis to patients. In this study, we present an update of testing results in a cohort of Argentinean non-syndromic hearing-impaired individuals. A total of 48 different sequence variants were detected in genomic DNA from patients referred to our laboratory. The y were manually curated and classified based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology ACMG/AMP standards and hearing-loss-gene-specific criteria of the ClinGen Hearing Loss Expert Panel. More than 50% of sequence variants were reclassified from their previous categorization in ClinVar. The se results provide an accurately interpreted set of variants to be taken into account by clinicians and the scientific community, and hence, aid the precise genetic counseling to patients. Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Bruque, Carlos David. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; Argentina Fil: Luce, Leonela Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Giliberto, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Lotersztein, Vanesa. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; Argentina Fil: Menazzi, Sebastián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Paoli, Bibiana Patricia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina

Published
2020

25. Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype–phenotype analysis in moderate cases

Author

Patricio O. Craig, Viviana Karina Dalamon, Raúl Reynoso Diamante, Enrique Mansilla, Ana Belén Elgoyhen, María E. Barteik, Bibiana Paoli, Vanesa Lotersztein, M. Florencia Wernert, and Carlos Curet

Subjects
Models, Molecular, Hearing loss, DNA Mutational Analysis, Molecular Sequence Data, Connexin, Deafness, Connexins, Genotype phenotype, Ciencias Biológicas, HEARING LOSS, Genética y Herencia, Audiometry, GJB6, Connexin 30, Genetics, medicine, Humans, Amino Acid Sequence, Molecular Biology, Alleles, Genetic Association Studies, DFNB1, biology, General Medicine, GJB2, Connexin 26, Mutation, biology.protein, Identification (biology), medicine.symptom, Gene Deletion, CIENCIAS NATURALES Y EXACTAS, Non syndromic
Abstract

This paper presents a mutation as well as a genotype-phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort. Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Wernert, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina Fil: Lotersztein, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina Fil: Reynoso, Raúl Alfredo. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Medicina. Centro Piloto de Deteccion de Errores Metabólicos; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro Otoaudiológico de Alta Tecnología; Argentina Fil: Barteik, María Eugenia. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Medicina. Centro Piloto de Deteccion de Errores Metabólicos; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro Otoaudiológico de Alta Tecnología; Argentina Fil: Curet, Carlos Augusto. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Medicina. Centro Piloto de Deteccion de Errores Metabólicos; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro Otoaudiológico de Alta Tecnología; Argentina Fil: Paoli, Bibiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Mansilla, Enrique. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina

Published
2013
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26. Connexin 26 (GJB2) mutation in an Argentinean patient with keratitis-ichthyosis-deafness (KID) syndrome: a case report

Author

Viviana Karina Dalamon, Ana Belén Elgoyhen, Paula Inés Buonfiglio, Patricio O. Craig, Keith A. Choate, Norma Pallares, Margarita Larralde, Vanesa Lotersztein, and Vicente Diamante

Subjects
Male, 0301 basic medicine, Connexin, Case Report, Medicina Clínica, Deafness, medicine.disease_cause, Connexins, 030207 dermatology & venereal diseases, 0302 clinical medicine, purl.org/becyt/ford/3.2 [https], Dry skin, Genetics(clinical), Genetics (clinical), Genetics, Mutation, GJB2, Connexin 26, medicine.anatomical_structure, Child, Preschool, purl.org/becyt/ford/3 [https], Medicina Critica y de Emergencia, medicine.symptom, Mutations, medicine.medical_specialty, CIENCIAS MÉDICAS Y DE LA SALUD, Argentina, hipoacusia, Biology, Keratitis, 03 medical and health sciences, otorhinolaryngologic diseases, medicine, Humans, Genetic Predisposition to Disease, dermatitis, Cytogenetics, p.Asp50Asn, Sequence Analysis, DNA, medicine.disease, Dermatology, Human genetics, 030104 developmental biology, Amino Acid Substitution, Scalp, Hypotrichosis, KID syndrome
Abstract

Background: Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare condition characterized by pre-lingual sensorineuraldeafness with skin hyperkeratinization. The primary cause of the disease is a loss-of-function mutation in the GJB2gene. Mutations in Argentinean patients have not been described.Case presentation: We studied a 2 year-old boy with bilateral congenital sensorineural deafness with dry skin over theentire body, hypotrichosis of the scalp, thin and light-blond hair. Analysis of the GJB2 gene nucleotide sequence revealedthe substitution of guanine-148 by adenine predicted to result in an Asp50Asn amino acid substitution.Conclusion: This is the first KID report in a patient from Argentina. This de novo mutation proved to be the cause ofkeratitis-ichthyosis-deafness syndrome (KID-syndrome) in the patient, and has implications in medical genetic practice Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Buonfiglio, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Larralde, Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Hospital Alemán; Argentina Fil: Craig, Patricio Oliver. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Lotersztein, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Choate, Keith. University of Yale; Estados Unidos Fil: Pallares, Norma. Instituto Superior de Implantes Cocleares “Dr. Vicente Diamante”; Argentina Fil: Diamante, Vicente. Instituto Superior de Implantes Cocleares “Dr. Vicente Diamante”; Argentina Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina

Published
2016
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