Child ; Developmental Disabilities ; diagnosis ; Humans ; Intellectual Disability ; diagnosis ; Male ; Neuronal Ceroid-Lipofuscinoses ; diagnosis

OBJECTIVE: To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7). METHODS: A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed. RESULTS: The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7. CONCLUSION Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
Male ; Female ; Humans ; Membrane Transport Proteins/genetics* ; Neuronal Ceroid-Lipofuscinoses/diagnosis* ; Retrospective Studies ; Atrophy ; Mutation

Neuronal ceroid lipofuscinoses (NCL) are the most common childhood neurodegenerative disorders. Clinical features include seizures, blindness, psychomotor deterioration, the age of onset differ for each NCL type. Diagnosis of late infantile NCL relies on the characteristic clinical presentation, electrophysiological and neuroradiological findings, and identification of the ultrastructural abnormalities. The Photoparoxsmal response provide diagnostic clues to an atypical case of Infantile NCL in which results of extraneuronal biopsies were negative and MRI findings resembles leukodystrophy. Photic stimulation with 2 to 5 Hz activity elicited discrete spike and wave discharges in the occipital region on electroencephalogram and no sleep spindles are present. In patients with rapid neurologic deterioration, diagnosis of NCL should be considered and an EEG must be performed using photic stimulation to look for characteristic findings.
Age of Onset ; Biopsy ; Blindness ; Diagnosis ; Electroencephalography* ; Humans ; Magnetic Resonance Imaging ; Neurodegenerative Diseases ; Neuronal Ceroid-Lipofuscinoses* ; Photic Stimulation ; Seizures

OBJECTIVETo search for possible novel mutations in palmitoyl-protein thioesterase 1 (PPT1) gene in two Chinese babies with infantile neuronal ceroid lipofuscinosis (INCL).

METHODSTwo probands with INCL, confirmed clinically and pathologically, were used for mutation search in PPT1 gene. Onset of the disease occurred before the age of 1 year and they mainly showed progressive mental and motor retardation. The 9 coding exons and their flanking intron sequences of palmitoyl-protein thioesterase 1 (PPT1) gene were amplified by using PCR and sequenced. The parents of proband 1 were also examined.

RESULTSOne splicing mutation and two missense mutations were identified in the two probands: the proband 1 carrying a compound heterozygous mutation of a IVS1 + 1G-->A mutation in intron 1 and a c550G-->A mutation in exon 6 leading to the amino acid substitution of E184K. Additionally, the parents of the proband 1 also harbored one of the mutations of the patient, respectively. The proband 2 carrying a homozygous mutation of c272A-->C in exon 3, which resulted in the amino acid substitutions of Q91P.

CONCLUSIONSThe IVS1 + 1G-->A mutation and Q91P mutation are novel mutations, which lead to INCL. The genetic abnormalities of PPT1 in Chinese patients may not be completely the same as those in the patients of other regions of the world.

Age of Onset ; Asian Continental Ancestry Group ; Base Sequence ; Child, Preschool ; Codon ; DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Intellectual Disability ; genetics ; physiopathology ; Introns ; Male ; Mutation ; Mutation, Missense ; Neuronal Ceroid-Lipofuscinoses ; diagnosis ; genetics ; physiopathology ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; RNA Splice Sites ; Thiolester Hydrolases ; genetics