Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation
Haploinsufficiency of <i>AUTS2</i> has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of &l...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/9/1360 |
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| author | Carolina Sanchez-Jimeno Fiona Blanco-Kelly Fermina López-Grondona Rebeca Losada-Del Pozo Beatriz Moreno María Rodrigo-Moreno Elena Martinez-Cayuelas Rosa Riveiro-Alvarez María Fenollar-Cortés Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera |
| author_facet | Carolina Sanchez-Jimeno Fiona Blanco-Kelly Fermina López-Grondona Rebeca Losada-Del Pozo Beatriz Moreno María Rodrigo-Moreno Elena Martinez-Cayuelas Rosa Riveiro-Alvarez María Fenollar-Cortés Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera |
| author_sort | Carolina Sanchez-Jimeno |
| collection | DOAJ |
| description | Haploinsufficiency of <i>AUTS2</i> has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of <i>AUTS2</i> is well established, clinical features of patients harboring <i>AUTS2</i> sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with <i>AUTS2</i> pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98% of patients, microcephaly in 65%, feeding difficulties in 62%, ADHD or hyperactivity in 54%, and autistic traits in 52%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3′ end of the gene, confirming the genotype-phenotype correlation initially described. |
| first_indexed | 2024-03-10T07:39:13Z |
| format | Article |
| id | doaj.art-f7acd3b8a87c4127bb72ba60628e41e4 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T07:39:13Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f7acd3b8a87c4127bb72ba60628e41e42023-11-22T13:13:52ZengMDPI AGGenes2073-44252021-08-01129136010.3390/genes12091360Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype CorrelationCarolina Sanchez-Jimeno0Fiona Blanco-Kelly1Fermina López-Grondona2Rebeca Losada-Del Pozo3Beatriz Moreno4María Rodrigo-Moreno5Elena Martinez-Cayuelas6Rosa Riveiro-Alvarez7María Fenollar-Cortés8Carmen Ayuso9Marta Rodríguez de Alba10Isabel Lorda-Sanchez11Berta Almoguera12Department of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Pediatrics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Pediatrics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Pediatrics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Pediatrics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainClinical Genetics Unit, Department of Clinical Analysis, Clínico San Carlos University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainDepartment of Genetics and Genomics, IIS–Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainHaploinsufficiency of <i>AUTS2</i> has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of <i>AUTS2</i> is well established, clinical features of patients harboring <i>AUTS2</i> sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with <i>AUTS2</i> pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98% of patients, microcephaly in 65%, feeding difficulties in 62%, ADHD or hyperactivity in 54%, and autistic traits in 52%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3′ end of the gene, confirming the genotype-phenotype correlation initially described.https://www.mdpi.com/2073-4425/12/9/1360<i>AUTS2</i>AUTS2 syndromeADHDneurodevelopmental disorderautism |
| spellingShingle | Carolina Sanchez-Jimeno Fiona Blanco-Kelly Fermina López-Grondona Rebeca Losada-Del Pozo Beatriz Moreno María Rodrigo-Moreno Elena Martinez-Cayuelas Rosa Riveiro-Alvarez María Fenollar-Cortés Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation Genes <i>AUTS2</i> AUTS2 syndrome ADHD neurodevelopmental disorder autism |
| title | Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation |
| title_full | Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation |
| title_fullStr | Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation |
| title_full_unstemmed | Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation |
| title_short | Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation |
| title_sort | attention deficit hyperactivity and autism spectrum disorders as the core symptoms of auts2 syndrome description of five new patients and update of the frequency of manifestations and genotype phenotype correlation |
| topic | <i>AUTS2</i> AUTS2 syndrome ADHD neurodevelopmental disorder autism |
| url | https://www.mdpi.com/2073-4425/12/9/1360 |
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