17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report
Abstract Background Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TB...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2017-10-01
|
Series: | BMC Medical Genetics |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12881-017-0479-3 |
id |
doaj-3a2aa9527448442697661b0790640a28 |
---|---|
record_format |
Article |
spelling |
doaj-3a2aa9527448442697661b0790640a282021-04-02T04:44:30ZengBMCBMC Medical Genetics1471-23502017-10-011811510.1186/s12881-017-0479-317q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case reportKaren Wessel0Jehan Suleiman1Tamam E. Khalaf2Shivendra Kishore3Arndt Rolfs4Ayman W. El-Hattab5Centogene AGDivision of Neurology, Department of Pediatrics, Tawam HospitalBiochemistry, University of Toronto MississaugaCentogene AGCentogene AGDivision of Clinical Genetics and Metabolic Disorders, Department of Pediatrics, Tawam HospitalAbstract Background Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region. Case presentation We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child. Conclusions The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication.http://link.springer.com/article/10.1186/s12881-017-0479-317q23.2q23.3 duplicationGenomic rearrangementsChromosomal microarrayChromosomal disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karen Wessel Jehan Suleiman Tamam E. Khalaf Shivendra Kishore Arndt Rolfs Ayman W. El-Hattab |
spellingShingle |
Karen Wessel Jehan Suleiman Tamam E. Khalaf Shivendra Kishore Arndt Rolfs Ayman W. El-Hattab 17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report BMC Medical Genetics 17q23.2q23.3 duplication Genomic rearrangements Chromosomal microarray Chromosomal disorders |
author_facet |
Karen Wessel Jehan Suleiman Tamam E. Khalaf Shivendra Kishore Arndt Rolfs Ayman W. El-Hattab |
author_sort |
Karen Wessel |
title |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
title_short |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
title_full |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
title_fullStr |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
title_full_unstemmed |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
title_sort |
17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report |
publisher |
BMC |
series |
BMC Medical Genetics |
issn |
1471-2350 |
publishDate |
2017-10-01 |
description |
Abstract Background Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region. Case presentation We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child. Conclusions The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication. |
topic |
17q23.2q23.3 duplication Genomic rearrangements Chromosomal microarray Chromosomal disorders |
url |
http://link.springer.com/article/10.1186/s12881-017-0479-3 |
work_keys_str_mv |
AT karenwessel 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport AT jehansuleiman 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport AT tamamekhalaf 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport AT shivendrakishore 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport AT arndtrolfs 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport AT aymanwelhattab 17q232q233denovoduplicationinassociationwithspeechandlanguagedisorderlearningdifficultiesincoordinationmotorskillimpairmentandbehavioraldisturbancesacasereport |
_version_ |
1724173031105888256 |