第十二届北京罕见病学术大会暨2024京津冀罕见病学术大会征文(065)

Yujia Zhang， Xiaojuan Tian， Hua Li， Xiuwei Zhuo， Fang Fang， Xiaotun Ren，

Changhong Ding，

Xiaohui Wang， Shuhua Chen， Jie Deng， Zhimei Liu， Weixing Feng，

Jianbo Zhao， Hong Jin， Hongmei Wang， Yun Wu，

Weihua Zhang， Wei Wei    Chunhong Chen

Department of Neurology， Beijing Children’s Hospital， Capital Medical University，

National Center of Children’s Health

Corresponding author: Chunhong Chen，

Yujia Zhang and Xiaojuan    contributed equally to this work

ABSTRACT

Human beta-propeller protein-associated neurodegeneration (BPAN) is a subtype of neurodegeneration with brain iron accumulation (NBIA)， caused by mutations in the WDR45 gene. This study analyzed the genotypes and phenotypes of WDR45 mutations in a Chinese cohort to widen the spectrum of WDR45 mutations. Among the 15 participants (4 males and 11 females) enrolled， 12 different WDR45 mutations (5 nonsense， 3 splicing defect， 1 missense， 1 frame shift， 1 start codon abolished， and 1 amino acid deletion) were identified. Notably， four of these mutations were novel (c.670_671del p.Q224Ifs*13， c.1008T>A p.Y336* ， c.229A>T p.I77F and c.1056C>A p.Y352*). One female participant’s mutation was inherited from her mother， while all the other participants’ mutations were confirmed to be de novo. Two mutations (c.400C>T p.R134* and c.700C>T p.R234*) were identified as recurrent hotspot mutations. The age of the participants at the time of the last follow-up ranged from 2 to 15 years (median age: 6 years). Among them， 13 (87%， 13/15) had seizures， 14 (93%， 14/15) had developmental delays， and 7 (47%， 7/15) had sleeping issues. Febrile seizures(62%， 8/13) and slow background of EEG (50%， 6/12) were observed in most participants and only one showed iron deposition through MRI. None of the participants exhibited neurological deterioration into dystonia， parkinsonism， or a new cognitive decline， but they all showed slow developmental gains over time.