Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene
| Title: | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
|---|---|
| Authors: | Jun Wang, Xinrong Sun, Lianying Jiao, Zhengtao Xiao, Farooq Riaz, Yufeng Zhang, Pengfei Xu, Ruiqing Liu, Tiantian Tang, Meiqi Liu, Dongmin Li |
| Source: | Frontiers in Genetics, Vol 13 (2022) |
| Publisher Information: | Frontiers Media S.A., 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Genetics |
| Subject Terms: | glycerol-3-phosphate dehydrogenase 1 (GPD1), transient infantile hypertriglyceridemia (HTGTI), hypertriglyceridemia, hepatic steatosis, hepatomegaly, Genetics, QH426-470 |
| More Details: | Objective: Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene and the effect of HTGTI on the protein structure of GPD1.Methods: Retrospective analysis, using the general data, symptoms, signs, and auxiliary examinations, was performed on patients with HTGTI, which were confirmed by genetic testing in our hospital and reported cases online. The clinical data were analyzed using statistical and bioinformatic approaches.Results: A total of 31 genetically confirmed HTGTI patients were collected from our hospital and cases reported in the literature. The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. All the patients had normal psychiatric status, but 22.6% of them presented growth retardation and short stature, 93.5% had hepatomegaly, and 16.1% had splenomegaly. Just a few children were reported with jaundice, cholestasis, and obesity (3.2–6.5%). The laboratory investigations showed that 96.8% of them had hypertriglyceridemia (HTG) with a median level of 3.1 (2.1, 5.5) mmol/L, but only 30.0% had returned to normal during follow-up. In addition, 93.5% of patients had elevated alanine aminotransferase (ALT) with an average level of 92.1 ± 43.5 U/L, while 38.7% had hypercholesterolemia. Upon abdominal imaging, all patients presented fatty liver and liver steatosis, with 66.7% of patients showing hepatic fibrosis. Statistical differences in triglyceride (TG) level were observed in the ≤6 months group compared with the older groups and in the 13 months to 6 years group with >6 years group (H = 22.02, P < 0.05). The restricted cubic spline model showed that severe HTG decreased in the early stage of infants to the normal level; however, it rebounded again to a mild or moderate level after the following days. The genetic test revealed that the main variant types of the GPD1 gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A.Conclusion: The common manifestations of HTGTI were HTG, hepatomegaly, elevated liver transaminases, and hepatic steatosis in early infancy. However, the recurrence of aberrant HTG may pose long-term detrimental effects on HTGTI patients. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1664-8021 |
| Relation: | https://www.frontiersin.org/articles/10.3389/fgene.2022.916672/full; https://doaj.org/toc/1664-8021 |
| DOI: | 10.3389/fgene.2022.916672 |
| Access URL: | https://doaj.org/article/0ca4fb85ad5a4892941b31ea3ce9c75c |
| Accession Number: | edsdoj.0ca4fb85ad5a4892941b31ea3ce9c75c |
| Database: | Directory of Open Access Journals |
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| Items | – Name: Title Label: Title Group: Ti Data: Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Jun+Wang%22">Jun Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Xinrong+Sun%22">Xinrong Sun</searchLink><br /><searchLink fieldCode="AR" term="%22Lianying+Jiao%22">Lianying Jiao</searchLink><br /><searchLink fieldCode="AR" term="%22Zhengtao+Xiao%22">Zhengtao Xiao</searchLink><br /><searchLink fieldCode="AR" term="%22Farooq+Riaz%22">Farooq Riaz</searchLink><br /><searchLink fieldCode="AR" term="%22Yufeng+Zhang%22">Yufeng Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Pengfei+Xu%22">Pengfei Xu</searchLink><br /><searchLink fieldCode="AR" term="%22Ruiqing+Liu%22">Ruiqing Liu</searchLink><br /><searchLink fieldCode="AR" term="%22Tiantian+Tang%22">Tiantian Tang</searchLink><br /><searchLink fieldCode="AR" term="%22Meiqi+Liu%22">Meiqi Liu</searchLink><br /><searchLink fieldCode="AR" term="%22Dongmin+Li%22">Dongmin Li</searchLink> – Name: TitleSource Label: Source Group: Src Data: Frontiers in Genetics, Vol 13 (2022) – Name: Publisher Label: Publisher Information Group: PubInfo Data: Frontiers Media S.A., 2022. – Name: DatePubCY Label: Publication Year Group: Date Data: 2022 – Name: Subset Label: Collection Group: HoldingsInfo Data: LCC:Genetics – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22glycerol-3-phosphate+dehydrogenase+1+%28GPD1%29%22">glycerol-3-phosphate dehydrogenase 1 (GPD1)</searchLink><br /><searchLink fieldCode="DE" term="%22transient+infantile+hypertriglyceridemia+%28HTGTI%29%22">transient infantile hypertriglyceridemia (HTGTI)</searchLink><br /><searchLink fieldCode="DE" term="%22hypertriglyceridemia%22">hypertriglyceridemia</searchLink><br /><searchLink fieldCode="DE" term="%22hepatic+steatosis%22">hepatic steatosis</searchLink><br /><searchLink fieldCode="DE" term="%22hepatomegaly%22">hepatomegaly</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22QH426-470%22">QH426-470</searchLink> – Name: Abstract Label: Description Group: Ab Data: Objective: Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene and the effect of HTGTI on the protein structure of GPD1.Methods: Retrospective analysis, using the general data, symptoms, signs, and auxiliary examinations, was performed on patients with HTGTI, which were confirmed by genetic testing in our hospital and reported cases online. The clinical data were analyzed using statistical and bioinformatic approaches.Results: A total of 31 genetically confirmed HTGTI patients were collected from our hospital and cases reported in the literature. The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. All the patients had normal psychiatric status, but 22.6% of them presented growth retardation and short stature, 93.5% had hepatomegaly, and 16.1% had splenomegaly. Just a few children were reported with jaundice, cholestasis, and obesity (3.2–6.5%). The laboratory investigations showed that 96.8% of them had hypertriglyceridemia (HTG) with a median level of 3.1 (2.1, 5.5) mmol/L, but only 30.0% had returned to normal during follow-up. In addition, 93.5% of patients had elevated alanine aminotransferase (ALT) with an average level of 92.1 ± 43.5 U/L, while 38.7% had hypercholesterolemia. Upon abdominal imaging, all patients presented fatty liver and liver steatosis, with 66.7% of patients showing hepatic fibrosis. Statistical differences in triglyceride (TG) level were observed in the ≤6 months group compared with the older groups and in the 13 months to 6 years group with >6 years group (H = 22.02, P < 0.05). The restricted cubic spline model showed that severe HTG decreased in the early stage of infants to the normal level; however, it rebounded again to a mild or moderate level after the following days. The genetic test revealed that the main variant types of the GPD1 gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A.Conclusion: The common manifestations of HTGTI were HTG, hepatomegaly, elevated liver transaminases, and hepatic steatosis in early infancy. 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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3389/fgene.2022.916672 Languages: – Text: English Subjects: – SubjectFull: glycerol-3-phosphate dehydrogenase 1 (GPD1) Type: general – SubjectFull: transient infantile hypertriglyceridemia (HTGTI) Type: general – SubjectFull: hypertriglyceridemia Type: general – SubjectFull: hepatic steatosis Type: general – SubjectFull: hepatomegaly Type: general – SubjectFull: Genetics Type: general – SubjectFull: QH426-470 Type: general Titles: – TitleFull: Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Jun Wang – PersonEntity: Name: NameFull: Xinrong Sun – PersonEntity: Name: NameFull: Lianying Jiao – PersonEntity: Name: NameFull: Zhengtao Xiao – PersonEntity: Name: NameFull: Farooq Riaz – PersonEntity: Name: NameFull: Yufeng Zhang – PersonEntity: Name: NameFull: Pengfei Xu – PersonEntity: Name: NameFull: Ruiqing Liu – PersonEntity: Name: NameFull: Tiantian Tang – PersonEntity: Name: NameFull: Meiqi Liu – PersonEntity: Name: NameFull: Dongmin Li IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 08 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 16648021 Numbering: – Type: volume Value: 13 Titles: – TitleFull: Frontiers in Genetics Type: main |
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