Novel SEPN1 Mutations in Exon 1 Are Common in Rigid Spine With Muscular Dystrophy Type 1 in Chinese Patients

Yanbin Fan; Zhifei Xu; Xing Li; Feng Gao; Enyu Guo; Xingzhi Chang; Cuijie Wei; Cheng Zhang; Qing Yu; Chengli Que; Jiangxi Xiao; Chuanzhu Yan; Zhaoxia Wang; Yun Yuan; Hui Xiong

doi:10.3389/fgene.2022.825793

Novel SEPN1 Mutations in Exon 1 Are Common in Rigid Spine With Muscular Dystrophy Type 1 in Chinese Patients

Front Genet. 2022 Mar 16:13:825793. doi: 10.3389/fgene.2022.825793. eCollection 2022.

Authors

Yanbin Fan¹, Zhifei Xu², Xing Li¹, Feng Gao³, Enyu Guo⁴, Xingzhi Chang¹, Cuijie Wei¹, Cheng Zhang⁵, Qing Yu⁵, Chengli Que⁵, Jiangxi Xiao⁶, Chuanzhu Yan⁷, Zhaoxia Wang⁸, Yun Yuan⁸, Hui Xiong¹

Affiliations

¹ Department of Pediatrics, Peking University First Hospital, Beijing, China.
² Department of General Pediatrics, Beijing Children's Hospital, Capital Medical University, Beijing, China.
³ Department of Neurology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁴ Department of Pediatrics, Jining No. 1 People's Hospital, Jining, China.
⁵ Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, China.
⁶ Department of Radiology, Peking University First Hospital, Beijing, China.
⁷ Department of Neurology, Qilu Hospital, Shandong University, Qingdao, China.
⁸ Department of Neurology, Peking University First Hospital, Beijing, China.

Abstract

Congenital muscular dystrophy with early rigid spine, also known as the rigid spine with muscular dystrophy type 1 (RSMD1), is caused by SEPN1 mutation. We investigated the clinical manifestations, pathological features, and genetic characteristics of 8 Chinese RSMD1 patients in order to improve diagnosis and management of the disease. Eight patients presented with delayed motor development, muscle weakness, hypotonia, and a myopathic face with high palatine arches. All patients could walk independently, though with poor running and jumping, and most had a rigid spine, lordosis, or scoliosis. The symptoms of respiratory involvement were present early, and upper respiratory tract infections and pneumonia often occurred. Five patients had severe pneumonia, pulmonary hypertension, and respiratory failure. Lung function tests showed variable restrictive ventilation dysfunction. Polysomnography suggested hypoxia and hypoventilation. The serum creatine kinase (CK) level was normal or mildly increased. Muscle biopsy indicated chronic myopathic changes and minicores. Muscle magnetic resonance imaging (MRI) showed diffuse fatty infiltration of the gluteus maximus and thigh muscle. SEPN1 gene analysis revealed 16 compound heterozygous variants, 81.3% of which are unreported, including 7 exon 1 variants. Our study expands the spectrum of clinical and genetic findings in RSMD1 to improve diagnosis, management, and standards of care. SEPN1 mutations in exon 1 are common and easily missed, and exon 1 should be carefully analyzed when RSMD1 is suspected, which will provide valuable genetic counseling for the family and useful information for future natural history studies and clinical trials.

Keywords: SEPN1 gene; congenital muscular dystrophy with spinal rigidity; respiratory insufficiency; rigid spine with muscular dystrophy type 1; selenoprotein N.