首页|PACS gene family-related neurological diseases:limited genotypes and diverse phenotypes

PACS gene family-related neurological diseases:limited genotypes and diverse phenotypes

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Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial abnormalities.Methods We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequenc-ing.Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients.Results With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACS1-related cases.Most patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3％,13/30),oxcarbazepine/carbamazepine(26.7％,8/30),and levetiracetam(20％,6/30).Almost all patients had intellectual disability/developmental delay.The most common pathogenic missense variants were PACS1 p.Arg203Trp and PACS2 p.Glu209Lys.In addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chrl4:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset epilepsy.Conclusions The clinical phenotypes of the different PACS heterozygous missense variants were similar.The pathogenic variant sites of PACS1 and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be pathogenic.These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

Developmental delayEpilepsyIntellectual disabilityPACS1PACS2

Han Zhang、Kai Gao、Shuang Wang、Yue-Hua Zhang、Zhi-Xian Yang、Ye Wu、Yu-Wu Jiang

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Department of Pediatrics,Peking University First Hospital,No.1 Xi'an Men Street,West District,Beijing 100034,China

Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases,Beijing,China

Children Epilepsy Center,Peking University First Hospital,Beijing,China

Key Laboratory for Neuroscience,Ministry of Education/National Health and Family Planning Commission,Peking University,Beijing,China

Center of Epilepsy,Beijing Institute for Brain Disorders,Beijing,China

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National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaKey Project of Clinical Medicine Research of National Clinical Research Center for Child Health and Disorders,Children's HospitaBeijing Natural Science FoundationBeijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic DiseasesCapital Health Research and Development of Special FundNational High Level Hospital Clinical Research Funding(Scientific Research Seed Fund of Peking University First Hospital)Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities

2020YFA0804000819712111202660681601131NCRCCHD-2021-KP-027212109BZ03172020-1-40712022SF29BMU2017JI002BMU2018XY006PKU2017LCX06

2024

10.1007/s12519-022-00652-z

世界儿科杂志(英文版)

世界儿科杂志(英文版)

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年,卷(期)：2024.20(1)
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