Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci. To date, several intellectual disability (ID) susceptibility genes have frequently been identified in ASD. Here, whole exome sequencing was carried out on a proband with A...
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.00061/full |
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| author | Areerat Hnoonual Potchanapond Graidist Potchanapond Graidist Supika Kritsaneepaiboon Pornprot Limprasert Pornprot Limprasert |
| author_facet | Areerat Hnoonual Potchanapond Graidist Potchanapond Graidist Supika Kritsaneepaiboon Pornprot Limprasert Pornprot Limprasert |
| author_sort | Areerat Hnoonual |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci. To date, several intellectual disability (ID) susceptibility genes have frequently been identified in ASD. Here, whole exome sequencing was carried out on a proband with ASD and identified compound heterozygous mutations of the TRAPPC9, which plays a role in the neuronal NF-κB signaling pathway. These mutations consisted of a novel frameshift mutation (c.2415_2416insC, p.His806Profs∗9) and a rare splice site mutation (c.3349+1G>A) that were segregated from an unaffected father and unaffected mother, respectively. These two heterozygous mutations were also identified in the patient’s older brother with ID. Quantitative RT-PCR revealed a significant reduction of TRAPPC9 transcript in two siblings. This study first describes compound heterozygous mutations of the TRAPPC9 gene in two siblings with ASD and ID, which is notable as only homozygous mutations or compound heterozygous for copy number variations and rare variant in this gene have been reported to date and associated with autosomal recessive intellectual disability. The two siblings carrying compound heterozygous TRAPPC9 mutations presented with ID, developmental delay, microcephaly and brain abnormalities similarly to the clinical features found in almost cases with homozygous TRAPPC9 mutation in previous studies. Together this study provides evidence that clinical manifestations of TRAPPC9 mutations as seen in our patients with ID and autism may be broader than previous case reports have indicated. |
| first_indexed | 2024-12-12T01:25:28Z |
| format | Article |
| id | doaj.art-e655817bae2c4720ab3ada5cdc52c52f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T01:25:28Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-e655817bae2c4720ab3ada5cdc52c52f2022-12-22T00:43:06ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-02-011010.3389/fgene.2019.00061413583Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual DisabilityAreerat Hnoonual0Potchanapond Graidist1Potchanapond Graidist2Supika Kritsaneepaiboon3Pornprot Limprasert4Pornprot Limprasert5Division of Human Genetics, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, ThailandDepartment of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Songkhla, ThailandThe Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Songkhla, ThailandDepartment of Radiology, Faculty of Medicine, Prince of Songkla University, Songkhla, ThailandDivision of Human Genetics, Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, ThailandFaculty of Medicine, King Mongkut’s Institute of Technology Ladkrabang, Bangkok, ThailandAutism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci. To date, several intellectual disability (ID) susceptibility genes have frequently been identified in ASD. Here, whole exome sequencing was carried out on a proband with ASD and identified compound heterozygous mutations of the TRAPPC9, which plays a role in the neuronal NF-κB signaling pathway. These mutations consisted of a novel frameshift mutation (c.2415_2416insC, p.His806Profs∗9) and a rare splice site mutation (c.3349+1G>A) that were segregated from an unaffected father and unaffected mother, respectively. These two heterozygous mutations were also identified in the patient’s older brother with ID. Quantitative RT-PCR revealed a significant reduction of TRAPPC9 transcript in two siblings. This study first describes compound heterozygous mutations of the TRAPPC9 gene in two siblings with ASD and ID, which is notable as only homozygous mutations or compound heterozygous for copy number variations and rare variant in this gene have been reported to date and associated with autosomal recessive intellectual disability. The two siblings carrying compound heterozygous TRAPPC9 mutations presented with ID, developmental delay, microcephaly and brain abnormalities similarly to the clinical features found in almost cases with homozygous TRAPPC9 mutation in previous studies. Together this study provides evidence that clinical manifestations of TRAPPC9 mutations as seen in our patients with ID and autism may be broader than previous case reports have indicated.https://www.frontiersin.org/article/10.3389/fgene.2019.00061/fullautismASDintellectual disabilitywhole exome sequencingTRAPPC9 |
| spellingShingle | Areerat Hnoonual Potchanapond Graidist Potchanapond Graidist Supika Kritsaneepaiboon Pornprot Limprasert Pornprot Limprasert Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability Frontiers in Genetics autism ASD intellectual disability whole exome sequencing TRAPPC9 |
| title | Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability |
| title_full | Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability |
| title_fullStr | Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability |
| title_full_unstemmed | Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability |
| title_short | Novel Compound Heterozygous Mutations in the TRAPPC9 Gene in Two Siblings With Autism and Intellectual Disability |
| title_sort | novel compound heterozygous mutations in the trappc9 gene in two siblings with autism and intellectual disability |
| topic | autism ASD intellectual disability whole exome sequencing TRAPPC9 |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.00061/full |
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