Genomic analysis for early diagnosis of atypical dyskinetic cerebral palsy
10.3760/cma.j.cn421666-20240910-00734
- VernacularTitle:基因检测在具有不随意运动型脑瘫表型相关疾病早期诊断中的临床应用
- Author:
Dianrong SUN
1
;
Guangmei CUI
;
Leihong ZHANG
;
Jianhui ZHAO
;
Rong YU
;
Mei HOU
Author Information
1. 青岛大学附属妇女儿童医院儿童康复中心，青岛 266011
- Publication Type:Journal Article
- Keywords:
Dyskinetic cerebral palsy;
Etiology;
Exome sequencing;
Molecular diagnosis;
Atypical cerebral palsy
- From:
Chinese Journal of Physical Medicine and Rehabilitation
2025;47(7):624-630
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To determine the genetic causes of dystonic cerebral palsy (DCP) of unknown etiology by using whole exome and mitochondrial gene detection methods, and to analyze clues for early identification of DCP.Methods:This was a retrospective analysis of clinical data describing 21 children with unknown etiology and DCP-like phenotypes. It involved collecting a detailed medical history, biochemical testing, neuroimaging, electroencephalography and hematuria metabolic screening. Peripheral blood was collected from the children, their parents and their siblings. Genomic DNA was extracted, and whole exome and/or mitochondrial gene sequencing was performed to obtain variant sites and annotations. The candidate variants were verified by Sanger sequencing.Results:No clear perinatal risk factors were found in the 21 cases, though there was 1 case of family history. Laboratory tests found increased lactic acid in 3 and abnormal thyroid function in 2 cases. The neuroimaging showed lesions in the basal ganglia in 2 cases, delayed myelination in 6 cases, sometimes with cortical dysplasia, a wide extracerebral space and/or a thin corpus callosum. The images of 11 of the children were normal. Later follow-up showed changes in the brain magnetic resonance images (MRIs) of 2 of the children. Pathogenic or likely pathogenic candidate variants were identified in 15 of the 21 children (71%) within 12 genes: TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MT- ATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 or NACC1. Fifteen of the children received a precise diagnosis. Genetic testing found heterozygous variants of ATP1 A2, SPR, ATP1 A3, MED13 L or NR4 A2 genes in the remaining six children, all of which were non-pathogenic variants. Conclusions:The absence of perinatal high-risk factors, a positive family history, and a normal or progressive brain MRI can be used as early clues to identify atypical DCP cases. TH, SLC16 A2, RHOBTB2, FOXG1, IFIH1, WDR45, MTATP6, KIAA2022, GNB1, GNAO1, SLC2 A1 and NACC1 variants belong to the spectrum of DCP-related pathogenic genes, and attention should be paid to the interpretation of genomic analysis results.
