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BMC Med Genet. 2019 May 7;20(1):76. doi: 10.1186/s12881-019-0811-1.

A Chinese pedigree with Brown-Vialetto-Van Laere syndrome due to two novel mutations of SLC52A2 gene: clinical course and response to riboflavin.

Shi K1,2, Shi Z1,3, Yan H1,3, Wang X4, Yang Y1, Xiong H1, Gu Q1, Wu Y1,3, Jiang Y5,6,7, Wang J8,9,10.

Author information

1
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
2
Department of Neurology, Children's Hospital of Shanxi, Taiyuan, 030013, China.
3
Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Peking University First Hospital, Beijing, 100034, China.
4
Cipher Gene, LCC, Beijing, 100080, China.
5
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China. jiangyw@263.net.
6
Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Peking University First Hospital, Beijing, 100034, China. jiangyw@263.net.
7
Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, 100034, China. jiangyw@263.net.
8
Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China. wang66jm@163.com.
9
Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases, Peking University First Hospital, Beijing, 100034, China. wang66jm@163.com.
10
Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, 100034, China. wang66jm@163.com.

Abstract

BACKGROUND:

Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by motor, sensory, and cranial neuronopathies, is mainly associated with defective riboflavin transporters encoded by SLC52A2 and SLC52A3 genes. Clinical outcomes have been shown to be improved significantly by high-dose riboflavin supplementation. The aim of this study was to identify genetic causes and further evaluate the clinical course and response to riboflavin in a Chinese pedigree with BVVLS.

CASE PRESENTATION:

We report the novel compound heterozygous variants c.1328G>A p.(Cys443Tyr) and c.1022_1023insC p. (Leu341Profs*103) of SLC52A2 gene in a female proband who presented in our out-patient clinic at the age of one-year-old with progressive mental and motor regression, breath holding, and brain stem dysfunction including facial weakness, hearing loss, dysphagia. Following high-dose riboflavin supplementation, the respiratory insufficiency and mental, motor, and bulbar function improved. However, sensorineural hearing loss was not improved. The missense variant site was highly conserved. Both variants were not found in the population database gnomAD. The two variants were inherited from her mother and father, respectively. Both variants were predicted to be deleterious by Polyphen2, Mutation taster, and SIFT and were classified as likely pathogenic according to the ACMG guideline.

CONCLUSIONS:

Two novel pathogenic variations of SLC52A2 gene were firstly found from a Chinese pedigree with BVVLS. Clinical outcomes could be improved by early diagnosis and riboflavin supplementation.

KEYWORDS:

Breath holding spells; Brown-Vialetto-Van Laere syndrome; SLC52A2; Sensorineural hearing loss

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