Resumen La displasia ectodérmica hipohidrótica (DEH) es un trastorno genético que se caracteriza ... more Resumen La displasia ectodérmica hipohidrótica (DEH) es un trastorno genético que se caracteriza por hipohidrosis, hipotricosis e hipodoncia. Comúnmente afecta a varones con una herencia recesiva ligada al X, aunque existen otras formas con herencia autosómica ...
BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, ... more BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.MethodsGenetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.Results128 individuals with causative variants inPITX2orFOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma forFOXC1-related ARS. Systemic anomalies were seen in all individuals withPITX2-related ARS and the majority of those withFOXC1-related ARS.PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum.FOXC1-related ARS exhibited characteristic hearing loss ...
ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a pati... more ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-li...
Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have dele... more Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his "gestalt." aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.
22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, w... more 22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11.2DS have congenital heart defects (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS patients that could be associated with the incomplete penetrance of CHD. Analysis of genomic DNA from 253 patients with 22q11.2DS using array technology showed an association between a microduplication located in region 17q21.31 and CHD (p-value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first three exons of KANSL1 gene. Bioinformatic analysis...
Deepika D'Cunha Burkardt | Anna Zachariou | Chey Loveday | Clare L. Allen | David J. Amor | A... more Deepika D'Cunha Burkardt | Anna Zachariou | Chey Loveday | Clare L. Allen | David J. Amor | Anna Ardissone | Siddharth Banka | Alexia Bourgois | Christine Coubes | Cheryl Cytrynbaum | Laurence Faivre | Gerard Marion | Rachel Horton | Dieter Kotzot | Guillermo Lay-Son | Melissa Lees | Karen Low | Ho-Ming Luk | Paul Mark | Allyn McConkie-Rosell | Marie McDonald | John Pappas | Christophe Phillipe | Deborah Shears | Brian Skotko | Fiona Stewart | Helen Stewart | I Karen. Temple | Frederic T. Mau-Them | Ricardo A. Verdugo | Rosanna Weksberg | Yuri A. Zarate | John M. Graham | Katrina Tatton-Brown
Andes pediatrica : revista Chilena de pediatria, 2021
In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry o... more In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry of Health requested advice from the Genetics Branch of the Chilean Society of Pediatrics, to define the level of prioritization for people with Down Syndrome . A panel of geneticists worked on the development of this consensus, in which not only patients with Down syndrome were included, but the search was extended to patients with other types of disabilities, in both pediatric and adult ages in or der to contribute to the development of public health measures against the COVID-19 pandemic. The consensus concludes that, given the prevalence of comorbidities associated with Down syndrome, the higher incidence of cases with severe COVID-19 in this population group and a higher mortality, individuals with trisomy 21 should be considered as a high-risk population, and therefore, vaccina tion against SARS-CoV-2 should have a high priority for all people with Down syndrome regardless of their a...
La esteogenesis imperfecta (OI) es un desorden que afecta la formacion del tejido oseo resultando... more La esteogenesis imperfecta (OI) es un desorden que afecta la formacion del tejido oseo resultando en una reduccion de la masa osea y propension a fracturas en un amplio rango de severidad clinica. En esta revision, analizamos los aspectos celulares y moleculares que podrian dar cuenta de esta tremenda variabilidad en el fenotipo de la OI de manera de comenzar a entender por que se producen estas diferencias entre los pacientes que padecen de esta enfermedad.
Resumen La displasia ectodérmica hipohidrótica (DEH) es un trastorno genético que se caracteriza ... more Resumen La displasia ectodérmica hipohidrótica (DEH) es un trastorno genético que se caracteriza por hipohidrosis, hipotricosis e hipodoncia. Comúnmente afecta a varones con una herencia recesiva ligada al X, aunque existen otras formas con herencia autosómica ...
BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, ... more BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.MethodsGenetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.Results128 individuals with causative variants inPITX2orFOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma forFOXC1-related ARS. Systemic anomalies were seen in all individuals withPITX2-related ARS and the majority of those withFOXC1-related ARS.PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum.FOXC1-related ARS exhibited characteristic hearing loss ...
ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a pati... more ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-li...
Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have dele... more Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his "gestalt." aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.
22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, w... more 22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11.2DS have congenital heart defects (CHD). The main goal of this study was to identify common CNVs in 22q11.2DS patients that could be associated with the incomplete penetrance of CHD. Analysis of genomic DNA from 253 patients with 22q11.2DS using array technology showed an association between a microduplication located in region 17q21.31 and CHD (p-value = 0.023, OR = 2.75, 95% CI = 1.17-7.03). This region includes the first three exons of KANSL1 gene. Bioinformatic analysis...
Deepika D'Cunha Burkardt | Anna Zachariou | Chey Loveday | Clare L. Allen | David J. Amor | A... more Deepika D'Cunha Burkardt | Anna Zachariou | Chey Loveday | Clare L. Allen | David J. Amor | Anna Ardissone | Siddharth Banka | Alexia Bourgois | Christine Coubes | Cheryl Cytrynbaum | Laurence Faivre | Gerard Marion | Rachel Horton | Dieter Kotzot | Guillermo Lay-Son | Melissa Lees | Karen Low | Ho-Ming Luk | Paul Mark | Allyn McConkie-Rosell | Marie McDonald | John Pappas | Christophe Phillipe | Deborah Shears | Brian Skotko | Fiona Stewart | Helen Stewart | I Karen. Temple | Frederic T. Mau-Them | Ricardo A. Verdugo | Rosanna Weksberg | Yuri A. Zarate | John M. Graham | Katrina Tatton-Brown
Andes pediatrica : revista Chilena de pediatria, 2021
In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry o... more In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry of Health requested advice from the Genetics Branch of the Chilean Society of Pediatrics, to define the level of prioritization for people with Down Syndrome . A panel of geneticists worked on the development of this consensus, in which not only patients with Down syndrome were included, but the search was extended to patients with other types of disabilities, in both pediatric and adult ages in or der to contribute to the development of public health measures against the COVID-19 pandemic. The consensus concludes that, given the prevalence of comorbidities associated with Down syndrome, the higher incidence of cases with severe COVID-19 in this population group and a higher mortality, individuals with trisomy 21 should be considered as a high-risk population, and therefore, vaccina tion against SARS-CoV-2 should have a high priority for all people with Down syndrome regardless of their a...
La esteogenesis imperfecta (OI) es un desorden que afecta la formacion del tejido oseo resultando... more La esteogenesis imperfecta (OI) es un desorden que afecta la formacion del tejido oseo resultando en una reduccion de la masa osea y propension a fracturas en un amplio rango de severidad clinica. En esta revision, analizamos los aspectos celulares y moleculares que podrian dar cuenta de esta tremenda variabilidad en el fenotipo de la OI de manera de comenzar a entender por que se producen estas diferencias entre los pacientes que padecen de esta enfermedad.
Chromosomal aberrations affect the functionality of certain genes and/or their regulatory element... more Chromosomal aberrations affect the functionality of certain genes and/or their regulatory elements, leading to congenital anomalies. Congenital ocular and oculofacial anomalies are frequent in this group of patients. This chapter describes the ocular and systemic anomalies resulting from isolated aberrations of chromosome number or structure involving a single chromosome, as detected by karyotype, fluorescence in situ hybridization or chromosomal microarray.
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Papers by Guillermo Lay-Son