Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression

UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive... BackgroundThe Upstream Binding Transcription Factor (UBTF) gene encodes two nucleolar proteins, UBTF1 and UBTF2. UBTF1 regulates rRNA transcription by RNA polymerase I, while UBTF2 regulates mRNA transcription by RNA polymerase II. A recurrent de novo dominant mutation c.628G>A (p.Glu210Lys) has been identified as a gain-of-function mutation associated with childhood onset neurodegeneration with brain atrophy (CONDBA). Evidence from large-scale population databases and Ubtf+/− mouse models indicates that UBTF haploinsufficiency is not tolerated.MethodsThree unrelated patients with global developmental delay and distinctive facial features were recruited for the study. Whole exome sequencing (WES) was performed to identify potential genetic abnormalities. Additionally, copy number variation analysis was conducted based on the WES data.ResultsAll three patients exhibited intellectual disabilities, social challenges and developmental delays in language and gross motor skills. Distinctive facial features included a wide forehead, sparse eyebrows, hypertelorism, narrow palpebral fissures, single-fold eyelids, a flat nasal bridge, anteverted nares, a long philtrum and a thin upper lip. Additionally, patient C presented with more severe language delay, recurrent hepatic dysfunction and an atrial septal defect. Patient A was found to have a nonsense variant, c.1327C>T (p.R443Ter), in the exon 13 of UBTF. Patients B and C both carried a heterozygous deletion encompassing the UBTF gene.ConclusionIn this study, we analysed the detailed phenotypes associated with UBTF haploinsufficiency, which, to our knowledge, have not been previously reported. We propose that UBTF haploinsufficiency-related global developmental delay and distinctive facial features, without neuroregression, constitute a new syndrome distinct from CONDBA. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Medical Genetics British Medical Journal

UBTF haploinsufficiency associated with UBTF-related global developmental delay and distinctive facial features without neuroregression

Download PDF
7 pages

Loading next page...
 
/lp/british-medical-journal/ubtf-haploinsufficiency-associated-with-ubtf-related-global-lMRUzCBX1w

References (35)

Publisher
British Medical Journal
Copyright
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
ISSN
0022-2593
eISSN
1468-6244
DOI
10.1136/jmg-2024-110061
Publisher site
See Article on Publisher Site

Abstract

BackgroundThe Upstream Binding Transcription Factor (UBTF) gene encodes two nucleolar proteins, UBTF1 and UBTF2. UBTF1 regulates rRNA transcription by RNA polymerase I, while UBTF2 regulates mRNA transcription by RNA polymerase II. A recurrent de novo dominant mutation c.628G>A (p.Glu210Lys) has been identified as a gain-of-function mutation associated with childhood onset neurodegeneration with brain atrophy (CONDBA). Evidence from large-scale population databases and Ubtf+/− mouse models indicates that UBTF haploinsufficiency is not tolerated.MethodsThree unrelated patients with global developmental delay and distinctive facial features were recruited for the study. Whole exome sequencing (WES) was performed to identify potential genetic abnormalities. Additionally, copy number variation analysis was conducted based on the WES data.ResultsAll three patients exhibited intellectual disabilities, social challenges and developmental delays in language and gross motor skills. Distinctive facial features included a wide forehead, sparse eyebrows, hypertelorism, narrow palpebral fissures, single-fold eyelids, a flat nasal bridge, anteverted nares, a long philtrum and a thin upper lip. Additionally, patient C presented with more severe language delay, recurrent hepatic dysfunction and an atrial septal defect. Patient A was found to have a nonsense variant, c.1327C>T (p.R443Ter), in the exon 13 of UBTF. Patients B and C both carried a heterozygous deletion encompassing the UBTF gene.ConclusionIn this study, we analysed the detailed phenotypes associated with UBTF haploinsufficiency, which, to our knowledge, have not been previously reported. We propose that UBTF haploinsufficiency-related global developmental delay and distinctive facial features, without neuroregression, constitute a new syndrome distinct from CONDBA.

Journal

Journal of Medical Genetics – British Medical Journal

Published: Oct 4, 2024

Keywords: Genetic Diseases, Inborn; Pediatrics; Neurology

There are no references for this article.