Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations

Wang,Yangyang; Chen,Xiang; Liu,Chan; Wu,Shamin; Xie,Qingfeng; Hu,Quan; Chen,Shan; Liu,Yiwei

doi:10.3892/etm.2019.7760

Metachromatic leukodystrophy: Characterization of two (p.Leu433Val, p.Gly449Arg) arylsulfatase A mutations

Authors:
- Yangyang Wang
- Xiang Chen
- Chan Liu
- Shamin Wu
- Qingfeng Xie
- Quan Hu
- Shan Chen
- Yiwei Liu
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Affiliations: Department of Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 9, 2019 https://doi.org/10.3892/etm.2019.7760
Pages: 1738-1744
Copyright : © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Metachromatic leukodystrophy disorder (MLD) is an autosomal recessive lysosomal storage disease. The disease is primarily caused by a deficiency in the enzyme arylsulfatase A (ASA), which is encoded by the ARSA gene. A total of 254 mutations have been reported in different populations. The present study aimed to detect causative gene mutations in an atypical case presenting with attention deficit hyperactivity disorder through whole‑exome sequencing. Of note, the patient's mother is from a consanguineous family. Compound heterozygous variants (c.1297C>G) + (c.1345G>A) [(p.Leu433Val) + (p.Gly449Arg)] were identified in exon 8 in the ARSA gene of the pediatric patient. The two missense mutations identified have not been previously reported, to the best of our knowledge. Furthermore, an in silico analysis and multiple phylogenetic tree analyses of ARSA homologs were performed to predict the effects of the two novel mutations. Serial changes were observed in the patient with MLD at follow‑up visits over 6 years. However, brain MRI images demonstrated no notable progression and the number of ASA enzymes was stable. Also, the results of neurodevelopmental assessment showed that the patient was diagnose with ADHD. These data may offer a potential explanation of the genotype‑phenotype correlation in MLD and enhance the spectrum of mutations associated with the condition.

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