Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 26, 2021; 9(30): 9302-9309
Published online Oct 26, 2021. doi: 10.12998/wjcc.v9.i30.9302
Missense mutation in DYNC1H1 gene caused psychomotor developmental delay and muscle weakness: A case report
Feng-Juan Ding, Gui-Zhen Lyu, Victor Wei Zhang, Hua Jin
Feng-Juan Ding, Hua Jin, Prenatal Diagnosis Center, Jinan Maternal and Child Health Hospital, Jinan 250001, Shandong Province, China
Gui-Zhen Lyu, Victor Wei Zhang, AmCare Genomics lab (Guangzhou), Guangzhou 510300, Guangdong Province, China
Victor Wei Zhang, Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77001, United States
Author contributions: Ding FJ treated the patient and wrote the manuscript; Lyu GZ reviewed the manuscript; Jin H and Zhang VW assisted in the revision and submission of the manuscript; all authors issued final approval for the version to be submitted.
Supported by Jinan Science and Technology Project, No. 201805014.
Informed consent statement: Informed written consent was obtained from the patient’s parents for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to report.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hua Jin, MD, Associate Chief Physician, Prenatal Diagnosis Center, Jinan Maternal and Child Health Hospital, No. 2 Jianguo Xiaojingsan Road, Shizhong District, Jinan 250001, Shandong Province, China. tonyshirly@163.com
Received: June 7, 2021
Peer-review started: June 7, 2021
First decision: June 25, 2021
Revised: July 9, 2021
Accepted: August 6, 2021
Article in press: August 6, 2021
Published online: October 26, 2021
Abstract
BACKGROUND

The DYNC1H1 gene encodes a part of the dynamic protein, and the protein mutations may further affect the growth and development of neurons, resulting in degeneration of anterior horn cells of the spinal cord, and a variety of clinical phenotypes finally resulting in axonal Charcot-Marie-Tooth disease type 20 (CMT20), mental retardation 13 (MRD13) and spinal muscular atrophy with lower extremity predominant 1 (SMA-LED). The incidence of the disease is low, and it is difficult to diagnose, especially in children. Here, we report a case of DYNC1H1 gene mutation and review the related literature to improve the pediatrician’s understanding of DYNC1H1 gene-related disease to make an early correct diagnosis and provide better services for children.

CASE SUMMARY

A 4-mo-old Chinese female child with adducted thumbs, high arch feet, and epileptic seizure presented slow response, delayed development, and low limb muscle strength. Electroencephalogram showed abnormal waves, a large number of multifocal sharp waves, sharp slow waves, and multiple spasms with a series of attacks. High-throughput sequencing and Sanger sequencing identified a heterozygous mutation, c.5885G>A (p.R1962H), in the DYNC1H1 gene (NM_001376) of the proband, which was not identified in her parents. Combined with the clinical manifestations and pedigree of this family, this mutation is likely pathogenic based on the American Academy of Medical Genetics and Genomics guidelines. The child was followed when she was 1 year and 2 mo old. The magnetic resonance imaging result was consistent with the findings of white matter myelinated dysplasia and congenital giant gyrus. The extensive neurogenic damage to the extremities was considered, as the results of electromyography showed that the motor conduction velocity and sensory conduction of the nerves of the extremities were not abnormal, and the degree of fit of the children with severe contraction was poor. At present, the child is 80 cm in length and 9 kg in weight, with slender limbs and low muscle strength, and still does not raise her head. She cannot sit or speak. Speech, motor, and mental development was significantly delayed. There is still no effective treatment for this disease.

CONCLUSION

We herein report a de novo variant of DYNC1H1 gene, c.5885G>A (p.R1962H), leading to overlapping phenotypes (seizure, general growth retardation, and muscle weakness) of CMT20, MRD13, and SMA-LED, but there is no effective treatment for such condition. Our case enriches the DYNC1H1 gene mutation spectrum and provides an important basis for clinical diagnosis and treatment and genetic counseling.

Keywords: DYNC1H1, Mental retardation, Muscle weakness, Medical exome sequencing, Case report

Core Tip: The dynein cytoplasmic1 heavy chain 1 gene-related diseases include Charcot-Marie-Tooth disease type 20, mental retardation 13, and spinal muscular atrophy with lower extremity predominant 1, all of which are inherited in an autosomal dominant manner. A novel mutation, c.5885G>A (p.R1962H) in the DYNC1H1 gene, led to overlapping phenotypes (seizure, general growth retardation, and muscle weakness) of those three diseases and expanded the DYNC1H1 gene mutation spectrum. And there is no effective treatment for such condition.