Genomic imbalances defining novel intellectual disability associated loci

F. tima Lopes, F. tima Torres, Gabriela Soares, Mafalda Barbosa, João Silva, Frederico Duque, Miguel Rocha, Joaquim Sá, Guiomar Oliveira, Maria João Sá, Teresa Temudo, Susana Sousa, Carla Marques, Sofia Lopes, Catarina Gomes, Gisela Barros, Arminda Jorge, Felisbela Rocha, Cecília Martins, Sandra Mesquita & 22 others Susana Loureiro, Elisa Maria Cardoso, Maria José Cálix, Andreia Dias, Cristina Martins, C. u R. Mota, Diana Antunes, Juliette Dupont, Sara Figueiredo, S. nia Figueiroa, Susana Gama-de-Sousa, Sara Cruz, Adriana Sampaio, Paul Eijk, Marjan M. Weiss, Bauke Ylstra, Paula Rendeiro, Purificação Tavares, Margarida Reis-Lima, Jorge Pinto-Basto, Ana Maria Fortuna, Patrícia Maciel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.
Original languageEnglish
Pages (from-to)164
JournalOrphanet Journal of Rare Diseases
Volume14
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Lopes, F. tima ; Torres, F. tima ; Soares, Gabriela ; Barbosa, Mafalda ; Silva, João ; Duque, Frederico ; Rocha, Miguel ; Sá, Joaquim ; Oliveira, Guiomar ; Sá, Maria João ; Temudo, Teresa ; Sousa, Susana ; Marques, Carla ; Lopes, Sofia ; Gomes, Catarina ; Barros, Gisela ; Jorge, Arminda ; Rocha, Felisbela ; Martins, Cecília ; Mesquita, Sandra ; Loureiro, Susana ; Cardoso, Elisa Maria ; Cálix, Maria José ; Dias, Andreia ; Martins, Cristina ; Mota, C. u R. ; Antunes, Diana ; Dupont, Juliette ; Figueiredo, Sara ; Figueiroa, S. nia ; Gama-de-Sousa, Susana ; Cruz, Sara ; Sampaio, Adriana ; Eijk, Paul ; Weiss, Marjan M. ; Ylstra, Bauke ; Rendeiro, Paula ; Tavares, Purificação ; Reis-Lima, Margarida ; Pinto-Basto, Jorge ; Fortuna, Ana Maria ; Maciel, Patrícia. / Genomic imbalances defining novel intellectual disability associated loci. In: Orphanet Journal of Rare Diseases. 2019 ; Vol. 14, No. 1. pp. 164.
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title = "Genomic imbalances defining novel intellectual disability associated loci",
abstract = "BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1{\%} of the patients, of which 5.2{\%} corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8{\%} of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.",
author = "Lopes, {F. tima} and Torres, {F. tima} and Gabriela Soares and Mafalda Barbosa and Jo{\~a}o Silva and Frederico Duque and Miguel Rocha and Joaquim S{\'a} and Guiomar Oliveira and S{\'a}, {Maria Jo{\~a}o} and Teresa Temudo and Susana Sousa and Carla Marques and Sofia Lopes and Catarina Gomes and Gisela Barros and Arminda Jorge and Felisbela Rocha and Cec{\'i}lia Martins and Sandra Mesquita and Susana Loureiro and Cardoso, {Elisa Maria} and C{\'a}lix, {Maria Jos{\'e}} and Andreia Dias and Cristina Martins and Mota, {C. u R.} and Diana Antunes and Juliette Dupont and Sara Figueiredo and Figueiroa, {S. nia} and Susana Gama-de-Sousa and Sara Cruz and Adriana Sampaio and Paul Eijk and Weiss, {Marjan M.} and Bauke Ylstra and Paula Rendeiro and Purifica{\cc}{\~a}o Tavares and Margarida Reis-Lima and Jorge Pinto-Basto and Fortuna, {Ana Maria} and Patr{\'i}cia Maciel",
year = "2019",
doi = "10.1186/s13023-019-1135-0",
language = "English",
volume = "14",
pages = "164",
journal = "Orphanet Journal of Rare Diseases",
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Lopes, FT, Torres, FT, Soares, G, Barbosa, M, Silva, J, Duque, F, Rocha, M, Sá, J, Oliveira, G, Sá, MJ, Temudo, T, Sousa, S, Marques, C, Lopes, S, Gomes, C, Barros, G, Jorge, A, Rocha, F, Martins, C, Mesquita, S, Loureiro, S, Cardoso, EM, Cálix, MJ, Dias, A, Martins, C, Mota, CUR, Antunes, D, Dupont, J, Figueiredo, S, Figueiroa, SN, Gama-de-Sousa, S, Cruz, S, Sampaio, A, Eijk, P, Weiss, MM, Ylstra, B, Rendeiro, P, Tavares, P, Reis-Lima, M, Pinto-Basto, J, Fortuna, AM & Maciel, P 2019, 'Genomic imbalances defining novel intellectual disability associated loci' Orphanet Journal of Rare Diseases, vol. 14, no. 1, pp. 164. https://doi.org/10.1186/s13023-019-1135-0, https://doi.org/10.1186/s13023-019-1135-0

Genomic imbalances defining novel intellectual disability associated loci. / Lopes, F. tima; Torres, F. tima; Soares, Gabriela; Barbosa, Mafalda; Silva, João; Duque, Frederico; Rocha, Miguel; Sá, Joaquim; Oliveira, Guiomar; Sá, Maria João; Temudo, Teresa; Sousa, Susana; Marques, Carla; Lopes, Sofia; Gomes, Catarina; Barros, Gisela; Jorge, Arminda; Rocha, Felisbela; Martins, Cecília; Mesquita, Sandra; Loureiro, Susana; Cardoso, Elisa Maria; Cálix, Maria José; Dias, Andreia; Martins, Cristina; Mota, C. u R.; Antunes, Diana; Dupont, Juliette; Figueiredo, Sara; Figueiroa, S. nia; Gama-de-Sousa, Susana; Cruz, Sara; Sampaio, Adriana; Eijk, Paul; Weiss, Marjan M.; Ylstra, Bauke; Rendeiro, Paula; Tavares, Purificação; Reis-Lima, Margarida; Pinto-Basto, Jorge; Fortuna, Ana Maria; Maciel, Patrícia.

In: Orphanet Journal of Rare Diseases, Vol. 14, No. 1, 2019, p. 164.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genomic imbalances defining novel intellectual disability associated loci

AU - Lopes, F. tima

AU - Torres, F. tima

AU - Soares, Gabriela

AU - Barbosa, Mafalda

AU - Silva, João

AU - Duque, Frederico

AU - Rocha, Miguel

AU - Sá, Joaquim

AU - Oliveira, Guiomar

AU - Sá, Maria João

AU - Temudo, Teresa

AU - Sousa, Susana

AU - Marques, Carla

AU - Lopes, Sofia

AU - Gomes, Catarina

AU - Barros, Gisela

AU - Jorge, Arminda

AU - Rocha, Felisbela

AU - Martins, Cecília

AU - Mesquita, Sandra

AU - Loureiro, Susana

AU - Cardoso, Elisa Maria

AU - Cálix, Maria José

AU - Dias, Andreia

AU - Martins, Cristina

AU - Mota, C. u R.

AU - Antunes, Diana

AU - Dupont, Juliette

AU - Figueiredo, Sara

AU - Figueiroa, S. nia

AU - Gama-de-Sousa, Susana

AU - Cruz, Sara

AU - Sampaio, Adriana

AU - Eijk, Paul

AU - Weiss, Marjan M.

AU - Ylstra, Bauke

AU - Rendeiro, Paula

AU - Tavares, Purificação

AU - Reis-Lima, Margarida

AU - Pinto-Basto, Jorge

AU - Fortuna, Ana Maria

AU - Maciel, Patrícia

PY - 2019

Y1 - 2019

N2 - BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.

AB - BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31277718

U2 - 10.1186/s13023-019-1135-0

DO - 10.1186/s13023-019-1135-0

M3 - Article

VL - 14

SP - 164

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

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