SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities
SOX5 encodes a conserved transcription factor implicated in cell-fate decisions of the neural lineage. SOX5 haploinsufficiency induced by larger genomic deletions has been linked to a recognizable pediatric syndrome combining developmental delay with intellectual disability, mild dysmorphism, inadeq...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Case Reports in Genetics |
| Online Access: | http://dx.doi.org/10.1155/2017/2721615 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564763904704512 |
|---|---|
| author | Michael Zech Katharina Poustka Sylvia Boesch Riccardo Berutti Tim M. Strom Wolfgang Grisold Werner Poewe Juliane Winkelmann |
| author_facet | Michael Zech Katharina Poustka Sylvia Boesch Riccardo Berutti Tim M. Strom Wolfgang Grisold Werner Poewe Juliane Winkelmann |
| author_sort | Michael Zech |
| collection | DOAJ |
| description | SOX5 encodes a conserved transcription factor implicated in cell-fate decisions of the neural lineage. SOX5 haploinsufficiency induced by larger genomic deletions has been linked to a recognizable pediatric syndrome combining developmental delay with intellectual disability, mild dysmorphism, inadequate behavior, and variable additional features including motor disturbances. In contrast to SOX5-involving deletions, examples of pathogenic SOX5 small coding variations are sparse in the literature and have been described only in singular cases with phenotypic abnormalities akin to those seen in the SOX5 microdeletion syndrome. Here a novel SOX5 loss-of-function point mutation, c.13C>T (p.Arg5X), is reported, identified in the course of exome sequencing applied to the diagnosis of an unexplained adult-onset motor disorder. Aged 43 years, our female index patient demonstrated abrupt onset of mixed generalized hyperkinesia, with dystonic and choreiform movements being the most salient features. The movement disorder was accompanied by behavioral problems such as anxiety and mood instability. The mutation was found to be inherited to the patient’s son who manifested abnormal behavior including diminished social functioning, paranoid ideation, and anxiety since adolescence. Our results expand the compendium of SOX5 damaging single-nucleotide variation mutations and suggest that SOX5 haploinsufficiency might not be restrictively associated with childhood-onset syndromic disease. |
| format | Article |
| id | doaj-art-8c267101d3844133988b9f45b8717be9 |
| institution | Kabale University |
| issn | 2090-6544 2090-6552 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Genetics |
| spelling | doaj-art-8c267101d3844133988b9f45b8717be92025-02-03T01:10:13ZengWileyCase Reports in Genetics2090-65442090-65522017-01-01201710.1155/2017/27216152721615SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral AbnormalitiesMichael Zech0Katharina Poustka1Sylvia Boesch2Riccardo Berutti3Tim M. Strom4Wolfgang Grisold5Werner Poewe6Juliane Winkelmann7Institut für Neurogenomik, Helmholtz Zentrum München, Munich, GermanyKaiser-Franz-Josef-Spital Wien, Vienna, AustriaDepartment of Neurology, Medical University Innsbruck, Innsbruck, AustriaInstitut für Humangenetik, Helmholtz Zentrum München, Munich, GermanyInstitut für Humangenetik, Helmholtz Zentrum München, Munich, GermanyKaiser-Franz-Josef-Spital Wien, Vienna, AustriaDepartment of Neurology, Medical University Innsbruck, Innsbruck, AustriaInstitut für Neurogenomik, Helmholtz Zentrum München, Munich, GermanySOX5 encodes a conserved transcription factor implicated in cell-fate decisions of the neural lineage. SOX5 haploinsufficiency induced by larger genomic deletions has been linked to a recognizable pediatric syndrome combining developmental delay with intellectual disability, mild dysmorphism, inadequate behavior, and variable additional features including motor disturbances. In contrast to SOX5-involving deletions, examples of pathogenic SOX5 small coding variations are sparse in the literature and have been described only in singular cases with phenotypic abnormalities akin to those seen in the SOX5 microdeletion syndrome. Here a novel SOX5 loss-of-function point mutation, c.13C>T (p.Arg5X), is reported, identified in the course of exome sequencing applied to the diagnosis of an unexplained adult-onset motor disorder. Aged 43 years, our female index patient demonstrated abrupt onset of mixed generalized hyperkinesia, with dystonic and choreiform movements being the most salient features. The movement disorder was accompanied by behavioral problems such as anxiety and mood instability. The mutation was found to be inherited to the patient’s son who manifested abnormal behavior including diminished social functioning, paranoid ideation, and anxiety since adolescence. Our results expand the compendium of SOX5 damaging single-nucleotide variation mutations and suggest that SOX5 haploinsufficiency might not be restrictively associated with childhood-onset syndromic disease.http://dx.doi.org/10.1155/2017/2721615 |
| spellingShingle | Michael Zech Katharina Poustka Sylvia Boesch Riccardo Berutti Tim M. Strom Wolfgang Grisold Werner Poewe Juliane Winkelmann SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities Case Reports in Genetics |
| title | SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities |
| title_full | SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities |
| title_fullStr | SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities |
| title_full_unstemmed | SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities |
| title_short | SOX5-Null Heterozygous Mutation in a Family with Adult-Onset Hyperkinesia and Behavioral Abnormalities |
| title_sort | sox5 null heterozygous mutation in a family with adult onset hyperkinesia and behavioral abnormalities |
| url | http://dx.doi.org/10.1155/2017/2721615 |
| work_keys_str_mv | AT michaelzech sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT katharinapoustka sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT sylviaboesch sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT riccardoberutti sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT timmstrom sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT wolfganggrisold sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT wernerpoewe sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities AT julianewinkelmann sox5nullheterozygousmutationinafamilywithadultonsethyperkinesiaandbehavioralabnormalities |