Dataset Information

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report.

ABSTRACT: INTRODUCTION:The AP4B1 gene encodes a subunit of adaptor protein complex-4 (AP4), a component of intracellular transportation of proteins which plays important roles in neurons. Bi-allelic mutations in AP4B1 cause autosomal recessive spastic paraplegia-47(SPG47). CASE PRESENTATION:Here we present a Chinese patient with spastic tetraplegia, moderate psychomotor development delay and febrile seizures plus. Brain MRIs showed dilated supratentorial ventricle, thin posterior and splenium part of corpus callosum. The patient had little progress through medical treatments and rehabilitating regimens. Whole exome sequencing identified novel compound heterozygous truncating variants c.1207C?>?T (p.Gln403*) and c.52_53delAC (p.Cys18Glnfs*7) in AP4B1 gene. Causal mutations in AP4B1 have been reported in 29 individuals from 22 families so far, most of which are homozygous mutations. CONCLUSIONS:Our study enriched the genetic and phenotypic spectrum of SPG47. Early discovery, diagnosis and proper treatment on the conditions generally increase chances of improvement on the quality of life for patients.

SUBMITTER: Ruan WC

PROVIDER: S-EPMC7071676 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report.

Ruan Wen-Cong WC Wang Jia J Yu Yong-Lin YL Che Yue-Ping YP Ding Li L Li Chen-Xi CX Wang Xiao-Dong XD Li Hai-Feng HF

BMC medical genetics 20200314 1

<h4>Introduction</h4>The AP4B1 gene encodes a subunit of adaptor protein complex-4 (AP4), a component of intracellular transportation of proteins which plays important roles in neurons. Bi-allelic mutations in AP4B1 cause autosomal recessive spastic paraplegia-47(SPG47).<h4>Case presentation</h4>Here we present a Chinese patient with spastic tetraplegia, moderate psychomotor development delay and febrile seizures plus. Brain MRIs showed dilated supratentorial ventricle, thin posterior and spleni ...[more]

PMID: 32171285

Similar Datasets

Project description:BackgroundThe 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 summaryA 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.ConclusionWe 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.

Dataset Information

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report.

Publications

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets