Cargando…

Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family

BACKGROUND: The serine active site-containing protein 1 (SERAC1) biallelic variant usually causes MEGDEL syndrome, clinically characterized by increased excretion of 3-methylglutaconic in the urine, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain MRI scans. In this study, w...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Dandan, Chen, Shaopei, Cai, Fengying, Shu, Jianbo, Zhi, Xiufang, Zheng, Jie, Zhang, Chunhua, Li, Dong, Cai, Chunquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873186/
https://www.ncbi.nlm.nih.gov/pubmed/35223715
http://dx.doi.org/10.3389/fped.2021.816265
_version_ 1784657411200516096
author Yan, Dandan
Chen, Shaopei
Cai, Fengying
Shu, Jianbo
Zhi, Xiufang
Zheng, Jie
Zhang, Chunhua
Li, Dong
Cai, Chunquan
author_facet Yan, Dandan
Chen, Shaopei
Cai, Fengying
Shu, Jianbo
Zhi, Xiufang
Zheng, Jie
Zhang, Chunhua
Li, Dong
Cai, Chunquan
author_sort Yan, Dandan
collection PubMed
description BACKGROUND: The serine active site-containing protein 1 (SERAC1) biallelic variant usually causes MEGDEL syndrome, clinically characterized by increased excretion of 3-methylglutaconic in the urine, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain MRI scans. In this study, we present a case from a Chinese family with disordered metabolism and dystonia owing to SERAC1 variants; the clinical phenotypes of the proband were different from those of MEGDEL syndrome but were similar to those juvenile-onset complicated hereditary spastic paraplegia. Thus, in this study, we aimed to confirm the relationship between SERAC1 variants and complicated hereditary spastic paraplegia. METHODS: MRI and laboratory tests, including gas chromatography/mass spectrometry (GC/MS), were carried out for the proband. Whole-exome sequencing was used to detect the candidate SERAC1 variants. Variants were verified using Sanger sequencing. Various software programs (PolyPhen-2, MutationTaster, PROVEAN, and SIFT) were used to predict the pathogenicity of novel variants. RESULTS: Brain MRI scans showed a symmetric flake abnormal signal shadow in the bilateral basal ganglia in T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) analyses. The excretion of 3-methylglutaconic acid was found to be increased in our GC/MS analysis. Whole-exome sequencing showed novel compound heterozygous variants, including a novel c.1495A>G (p.Met499Val) variant in exon 14 of SERAC1 inherited from the father and a novel c.721_722delAG (p.Leu242fs) variant in exon 8 inherited from the mother. The pathogenicity prediction results showed that these two variants were deleterious. CONCLUSIONS: This study presented a patient with complicated hereditary spastic paraplegia caused by SERAC1 variants. These findings expand the number of known SERAC1 variants and the phenotypic spectrum associated with SERAC1 deficiency. This study may contribute to counseling and prevention of hereditary diseases through prenatal.
format Online
Article
Text
id pubmed-8873186
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-88731862022-02-26 Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family Yan, Dandan Chen, Shaopei Cai, Fengying Shu, Jianbo Zhi, Xiufang Zheng, Jie Zhang, Chunhua Li, Dong Cai, Chunquan Front Pediatr Pediatrics BACKGROUND: The serine active site-containing protein 1 (SERAC1) biallelic variant usually causes MEGDEL syndrome, clinically characterized by increased excretion of 3-methylglutaconic in the urine, muscle hypotonia, sensorineural deafness, and Leigh-like lesions on brain MRI scans. In this study, we present a case from a Chinese family with disordered metabolism and dystonia owing to SERAC1 variants; the clinical phenotypes of the proband were different from those of MEGDEL syndrome but were similar to those juvenile-onset complicated hereditary spastic paraplegia. Thus, in this study, we aimed to confirm the relationship between SERAC1 variants and complicated hereditary spastic paraplegia. METHODS: MRI and laboratory tests, including gas chromatography/mass spectrometry (GC/MS), were carried out for the proband. Whole-exome sequencing was used to detect the candidate SERAC1 variants. Variants were verified using Sanger sequencing. Various software programs (PolyPhen-2, MutationTaster, PROVEAN, and SIFT) were used to predict the pathogenicity of novel variants. RESULTS: Brain MRI scans showed a symmetric flake abnormal signal shadow in the bilateral basal ganglia in T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) analyses. The excretion of 3-methylglutaconic acid was found to be increased in our GC/MS analysis. Whole-exome sequencing showed novel compound heterozygous variants, including a novel c.1495A>G (p.Met499Val) variant in exon 14 of SERAC1 inherited from the father and a novel c.721_722delAG (p.Leu242fs) variant in exon 8 inherited from the mother. The pathogenicity prediction results showed that these two variants were deleterious. CONCLUSIONS: This study presented a patient with complicated hereditary spastic paraplegia caused by SERAC1 variants. These findings expand the number of known SERAC1 variants and the phenotypic spectrum associated with SERAC1 deficiency. This study may contribute to counseling and prevention of hereditary diseases through prenatal. Frontiers Media S.A. 2022-02-11 /pmc/articles/PMC8873186/ /pubmed/35223715 http://dx.doi.org/10.3389/fped.2021.816265 Text en Copyright © 2022 Yan, Chen, Cai, Shu, Zhi, Zheng, Zhang, Li and Cai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Yan, Dandan
Chen, Shaopei
Cai, Fengying
Shu, Jianbo
Zhi, Xiufang
Zheng, Jie
Zhang, Chunhua
Li, Dong
Cai, Chunquan
Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title_full Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title_fullStr Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title_full_unstemmed Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title_short Complicated Hereditary Spastic Paraplegia Caused by SERAC1 Variants in a Chinese Family
title_sort complicated hereditary spastic paraplegia caused by serac1 variants in a chinese family
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873186/
https://www.ncbi.nlm.nih.gov/pubmed/35223715
http://dx.doi.org/10.3389/fped.2021.816265
work_keys_str_mv AT yandandan complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT chenshaopei complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT caifengying complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT shujianbo complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT zhixiufang complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT zhengjie complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT zhangchunhua complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT lidong complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily
AT caichunquan complicatedhereditaryspasticparaplegiacausedbyserac1variantsinachinesefamily