[Clinical and genetic analysis of a family with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation].

Objective: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare autosomal recessive disease. Affected individuals are invariably compound heterozygous for two mutations in DARS2. No reports of LBSL patients have been published in the mainland of China. The aim of this study was to explore the clinical and genetic features of a family with LBSL, which may contribute to definite diagnosis, genetic counseling and prenatal diagnosis of this rare disease in China.
Methods: Clinical data of the proband and other family members as well as DNA samples were collected. Clinical features including symptoms, signs and cranial MRI were analyzed. All 17 exons and exon-intron boundaries of DARS2 gene were amplified with polymerase chain reaction (PCR) and directly sequenced for genomic DNA. The mutation was proved by DNA restriction enzyme digestion of PCR-amplified fragments.
Results: (1) The clinical features of patient with LBSL included slowly progressive cerebellar ataxia and spasticity, the neurologic dysfunction involving the legs more than the arms, and with characteristic abnormalities observed on brain and spinal cord MRI. (2) Two mutations were identified, one was a novel missense mutation [c.665 G > A(p.Gly222Asp)] in DARS2 gene exon 8, the other (c.228-16 C > G) was in DARS2 gene intron 3.
Conclusion: This is the first report on LBSL patient and DARS2 mutation in China. p.Gly222Asp mutation is a novel mutation not reported around the world yet.