Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta
Abstract Background Intellectual disability is a complex multi‐faceted condition with diverse underlying etiologies. One rare form of intellectual disability is secondary to the loss of TRAPPC9, an activator of NF‐κB and a mediator of intracellular protein processing and trafficking. TRAPPC9 deficie...
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doaj-9dc5fbd2657f41b093711c9db7a0156c2020-11-25T02:10:06ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-05-0185n/an/a10.1002/mgg3.1211Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from MaltaKatelynn M. Wilton0Lauren B. Gunderson1Linda Hasadsri2Christopher P. Wood3Lisa A. Schimmenti4Mayo Clinic Alix School of Medicine Medical Scientist Training Program Mayo Clinic Rochester MN USADepartment of Clinical Genomics Mayo Clinic Rochester MN USADepartment of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USADepartment of Radiology Mayo Clinic Rochester MN USADepartment of Clinical Genomics Mayo Clinic Rochester MN USAAbstract Background Intellectual disability is a complex multi‐faceted condition with diverse underlying etiologies. One rare form of intellectual disability is secondary to the loss of TRAPPC9, an activator of NF‐κB and a mediator of intracellular protein processing and trafficking. TRAPPC9 deficiency has been described in 48 patients with more than 15 pathologic variants. Method Clinical evaluation, magnetic resonance imaging, and whole‐exome sequencing were used to characterize the underlying cause of absent speech, restricted/repetitive behaviors, and worsening behavioral outbursts in 27‐year‐old man from Malta. Results Magnetic Resonance Imaging showed morphologic abnormalities, including global cerebral and cerebellar hypoplasia. Genetic analysis through Whole Exome Sequencing identified a homozygous deletion (c.568_574del) in TRAPPC9 resulting in a frameshift, premature stop codon, and ultimately a truncated protein (p.Trp190Argfs*95). In this case, the pathogenic variant was homozygous, identified in both of the parents without known consanguinity. Conclusion Given the phenotype and genotype consistent with a deficiency in TRAPPC9, it is likely that this patient represents a novel case of this rare genetic syndrome. Specifically, this case, in the context of 48 total reported patients, raises questions as to the geographic origin of the pathologic variant and optimal detection and therapeutic intervention for this condition.https://doi.org/10.1002/mgg3.1211autism spectrum disordergenetic diseaseIDT13intellectual disabilityMRT13TRAPPC9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katelynn M. Wilton Lauren B. Gunderson Linda Hasadsri Christopher P. Wood Lisa A. Schimmenti |
spellingShingle |
Katelynn M. Wilton Lauren B. Gunderson Linda Hasadsri Christopher P. Wood Lisa A. Schimmenti Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta Molecular Genetics & Genomic Medicine autism spectrum disorder genetic disease IDT13 intellectual disability MRT13 TRAPPC9 |
author_facet |
Katelynn M. Wilton Lauren B. Gunderson Linda Hasadsri Christopher P. Wood Lisa A. Schimmenti |
author_sort |
Katelynn M. Wilton |
title |
Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta |
title_short |
Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta |
title_full |
Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta |
title_fullStr |
Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta |
title_full_unstemmed |
Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta |
title_sort |
profound intellectual disability caused by homozygous trappc9 pathogenic variant in a man from malta |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2020-05-01 |
description |
Abstract Background Intellectual disability is a complex multi‐faceted condition with diverse underlying etiologies. One rare form of intellectual disability is secondary to the loss of TRAPPC9, an activator of NF‐κB and a mediator of intracellular protein processing and trafficking. TRAPPC9 deficiency has been described in 48 patients with more than 15 pathologic variants. Method Clinical evaluation, magnetic resonance imaging, and whole‐exome sequencing were used to characterize the underlying cause of absent speech, restricted/repetitive behaviors, and worsening behavioral outbursts in 27‐year‐old man from Malta. Results Magnetic Resonance Imaging showed morphologic abnormalities, including global cerebral and cerebellar hypoplasia. Genetic analysis through Whole Exome Sequencing identified a homozygous deletion (c.568_574del) in TRAPPC9 resulting in a frameshift, premature stop codon, and ultimately a truncated protein (p.Trp190Argfs*95). In this case, the pathogenic variant was homozygous, identified in both of the parents without known consanguinity. Conclusion Given the phenotype and genotype consistent with a deficiency in TRAPPC9, it is likely that this patient represents a novel case of this rare genetic syndrome. Specifically, this case, in the context of 48 total reported patients, raises questions as to the geographic origin of the pathologic variant and optimal detection and therapeutic intervention for this condition. |
topic |
autism spectrum disorder genetic disease IDT13 intellectual disability MRT13 TRAPPC9 |
url |
https://doi.org/10.1002/mgg3.1211 |
work_keys_str_mv |
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