关键词: 婴儿神经轴索营养不良；　PLA2G6 基因；　基因突变；　临床特征

Abstract: 　Objective　To explore clinical features and PLA2G6 gene mutation characteristics of infantile neuroaxonal dystrophy (INAD) in 2 siblings. Method　The clinical data of INAD diagnosed by gene detection were reviewed and analyzed. Results　Onset of symptoms started at 2 year and 4 months in the younger brother and 1 year and 2 months in older sister, both of them acquired appropriate motor and cognitive milestones for age. Both of them presented motor and speech regression. With the younger brother, the progression of the disease was rapider than older sister, for him walking ability was lost at 3 years old, speech ability was lost at 5 years old. For the older sister, despite earlier onset, progression of the disease was slower that rapid motor and speech regression occurred until the age of 4. She lost walking and speaking ability at 5 years old, so far she is 11 year and 7 months old, still alive. Both of them had muscular hypertonia, spastic paralysis and positive pathological signs, but visual acuity, hearing and cognitive impairment was mild. Our patients show classic radiological features of INAD: cerebellar cortical atrophy with involvement of vermis and hemisphere. MRI for the older sister MRI showed bilateral and symmetrical T2/FLAIR hypointense signal changes in globus pallidus (brain iron accumulation). The genetic study revealed compound heterozygous mutations, a c.1993A>G (p.Met665Val) inherited from father and a c.28dupA (p.Thr 10Asnfs Ter11) inherited from mother in PLA2G6 gene, respectively. Furthermore, silico analysis predicted these variant can alter protein structure and function. Conclusions　This report has expanded the gene mutation spectrum of Chinese INAD patients. A novel mutation c.1993A>G in PLA2G6 gene may cooperate with the known pathogenic c.28dupA mutation to result in the autosomal recessive disorder of INAD.

Key words: infantile neuroaxonal dystrophy;　PLA2G6 gene;　genetic mutation;　clinical feature