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A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome

Heterozygous deletions at 19q12–q13.11 affecting TSHZ3, the teashirt zinc finger homeobox 3, have been associated with intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT), and postnatal growth retardation in humans and mice. TSHZ3 encodes a tr...

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Autores principales: Feichtinger, René G., Preisel, Martin, Steinbrücker, Katja, Brugger, Karin, Radda, Alexandra, Wortmann, Saskia B., Mayr, Johannes A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778592/
https://www.ncbi.nlm.nih.gov/pubmed/36553458
http://dx.doi.org/10.3390/genes13122191
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author Feichtinger, René G.
Preisel, Martin
Steinbrücker, Katja
Brugger, Karin
Radda, Alexandra
Wortmann, Saskia B.
Mayr, Johannes A.
author_facet Feichtinger, René G.
Preisel, Martin
Steinbrücker, Katja
Brugger, Karin
Radda, Alexandra
Wortmann, Saskia B.
Mayr, Johannes A.
author_sort Feichtinger, René G.
collection PubMed
description Heterozygous deletions at 19q12–q13.11 affecting TSHZ3, the teashirt zinc finger homeobox 3, have been associated with intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT), and postnatal growth retardation in humans and mice. TSHZ3 encodes a transcription factor regulating the development of neurons but is ubiquitously expressed. Using exome sequencing, we identified a heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in TSHZ3 in a 7-year-old girl with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis. The variant was present on the paternal TSHZ3 allele. The DNA from the father was not available for testing. This is the first report of a heterozygous point mutation in TSHZ3 causing the same phenotype as reported for monoallelic deletions in the same region. This confirms TSHZ3 as a novel disease gene for neurodevelopmental disorder in combination with behavioural issues and CAKUT.
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spelling pubmed-97785922022-12-23 A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome Feichtinger, René G. Preisel, Martin Steinbrücker, Katja Brugger, Karin Radda, Alexandra Wortmann, Saskia B. Mayr, Johannes A. Genes (Basel) Case Report Heterozygous deletions at 19q12–q13.11 affecting TSHZ3, the teashirt zinc finger homeobox 3, have been associated with intellectual disability and behavioural issues, congenital anomalies of the kidney and urinary tract (CAKUT), and postnatal growth retardation in humans and mice. TSHZ3 encodes a transcription factor regulating the development of neurons but is ubiquitously expressed. Using exome sequencing, we identified a heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in TSHZ3 in a 7-year-old girl with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis. The variant was present on the paternal TSHZ3 allele. The DNA from the father was not available for testing. This is the first report of a heterozygous point mutation in TSHZ3 causing the same phenotype as reported for monoallelic deletions in the same region. This confirms TSHZ3 as a novel disease gene for neurodevelopmental disorder in combination with behavioural issues and CAKUT. MDPI 2022-11-23 /pmc/articles/PMC9778592/ /pubmed/36553458 http://dx.doi.org/10.3390/genes13122191 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Feichtinger, René G.
Preisel, Martin
Steinbrücker, Katja
Brugger, Karin
Radda, Alexandra
Wortmann, Saskia B.
Mayr, Johannes A.
A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title_full A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title_fullStr A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title_full_unstemmed A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title_short A TSHZ3 Frame-Shift Variant Causes Neurodevelopmental and Renal Disorder Consistent with Previously Described Proximal Chromosome 19q13.11 Deletion Syndrome
title_sort tshz3 frame-shift variant causes neurodevelopmental and renal disorder consistent with previously described proximal chromosome 19q13.11 deletion syndrome
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778592/
https://www.ncbi.nlm.nih.gov/pubmed/36553458
http://dx.doi.org/10.3390/genes13122191
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