QRICH1 mutations cause a chondrodysplasia with developmental delay
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in QRICH1. In vitro studies confirmed that the mutation impaired expression of the QRICH1 protein. SiRNA-mediated knockdown of Qrich1 in primary mouse epiphyseal chondrocytes caused downregulation of gene expression associated with hypertrophic differentiation. We then identified an unrelated individual with another heterozygous de novo nonsense mutation in QRICH1 who had a similar phenotype. A recently published study identified QRICH1 mutations in three patients with developmental delay, one of whom had short stature. Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
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| Enthalten in: |
Clinical genetics - 95(2019), 1 vom: 01. Jan., Seite 160-164 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lui, Julian C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.02.2020 Date Revised 13.03.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cge.13457 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM289166802 |
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| 520 | |a © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in QRICH1. In vitro studies confirmed that the mutation impaired expression of the QRICH1 protein. SiRNA-mediated knockdown of Qrich1 in primary mouse epiphyseal chondrocytes caused downregulation of gene expression associated with hypertrophic differentiation. We then identified an unrelated individual with another heterozygous de novo nonsense mutation in QRICH1 who had a similar phenotype. A recently published study identified QRICH1 mutations in three patients with developmental delay, one of whom had short stature. Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Lee, Audrey |e verfasserin |4 aut | |
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| 700 | 1 | |a Vogt, Karen S |e verfasserin |4 aut | |
| 700 | 1 | |a Baron, Jeffrey |e verfasserin |4 aut | |
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