MFSD8 gene mutation and clinical characteristics of a family with neuronal ceroid lipofuscinosis type 7 / 中华神经科杂志

ABSTRACT

Objective:To investigate the clinical characteristics and mutation of MFSD8 gene in a family with neuronal ceroid lipofuscinosis type7 (CLN7).Methods:The clinical data of a CLN7 patient and her family from the Children′s Hospital Affiliated to Zhengzhou University in January 2018 were reviewed and analyzed. Whole exome sequencing of second-generation sequencing was used to analyze gene mutation results.Results:The proband, a five years and nine months old girl, admitted to the Children′s Hospital Affiliated to Zhengzhou University with the chief complaint of "intermittent seizures for seven months". She had the first seizure at the age of five years and two months, and different types of generalized tonic-clonic and atypical absence seizures were found. At the age of five years and nine months, she was admitted to the hospital with mild mental deterioration. She had normal motor and physical development. Ophthalmological evaluation revealed macular degeneration. The video electroencephalography revealed multifocal spikes or spike-and-wave, prominent in the anterior fronto-temporal regions. Magnetic resonance imaging (MRI) revealed cerebellar atrophy. Compound heterozygous mutations c.553 (exon 6) G>A and c.1391 (exon 13) C>T were found on her MFSD8 gene, supporting the diagnosis of CLN7. Each of her parent carried one of the mutations, and c.553 (exon 6) G>A was a new mutation. Her elder brother had the first seizure at the age of 6 years, with motor and mental deterioration as well as visual impairment. MRI revealed generalized cerebral atrophy. He had the same compound heterozygous mutations with his sister. No pathogenic mutation was found in her younger brother.Conclusions:CLN7 is a rare neurodegenerative disease, the main clinical features of which are epileptic seizures, progressive motor intelligence regression, visual loss, cranial MRI suggesting brain atrophy, and binocular macular degeneration. MFSD8 gene heterozygous mutations c.553G>A (p.V185I) and c.1391C>T (p.A464V) are the genetic etiology of this proband.