First case of genetically confirmed CLN3 disease in Chinese with cDNA sequencing revealing pathogenicity of a novel splice site variant.

BACKGROUND: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is a hereditary progressive neurodegenerative disease well documented among Caucasians, but such clinical data and genetic characterization is lacking among Asian populations. PATIENT AND METHODS: A 13-year-old Chinese girl presented for diagnostic evaluation with retinitis pigmentosa, generalised tonic-clonic seizure and cerebellar ataxia. Electron microscopy of whole blood and skin biopsy, and mutation analysis of CLN3 gene with genomic DNA and cDNA, were performed. RESULTS: Electron microscopy showed vacuolated lymphocytes, and characteristic patterns in eccrine glands suggestive of neuronal ceroid lipofuscinosis. Sequencing of genomic DNA showed homozygous splice site variant NM_000086.2(CLN3):c.906+6T>G, and the pathogenicity of which was confirmed by cDNA sequencing to demonstrate the deletion of a transmembrane domain of the CLN3 protein. The mutant protein was predicted to adversely affect ligand binding of CLN3 as a lysosomal membrane protein. CONCLUSIONS: Here we report the first genetically confirmed CLN3 disease in Chinese, with a novel splice site variant with proposed pathogenetic mechanism relating gene and protein, and highlights the potential ethnic differences in the mutation spectrum. We wish to establish the importance of clinical awareness and laboratory diagnosis of CLN3 disease, especially in the promising age of gene therapy.

Motor ability and weight status are determinants of out-of-school activity participation for children with developmental coordination disorder.

According to the International Classification of Functioning, Disability and Health model endorsed by the World Health Organization, participation in everyday activities is integral to normal child development. However, little is known about the influence of motor ability and weight status on physical activity participation in children with developmental coordination disorder (DCD). This study aimed to (1) compare motor performance, weight status and pattern of out-of-school activity participation between children with DCD and those without; and (2) identify whether motor ability and weight status were determinants of participation patterns among children with DCD. We enrolled 81 children with DCD (boys, n = 63; girls, n = 18; mean age, 8.07 ± 1.5 years) and 67 typically developing children (boys, n = 48; girls, n = 19; mean age, 8.25 ± 1.6 years). Participation patterns (diversity, intensity, companionship, location, and enjoyment) were evaluated with the Children Assessment of Participation and Enjoyment. Motor ability was evaluated with the Movement Assessment Battery for Children, second edition (MABC-2). Other factors that may influence participation such as age, gender, and body weight were also recorded. Analysis of variance was used to compare outcome variables of the two groups, and significant determinants of activity participation were identified by multiple regression analysis. Children with DCD participated in fewer activities (i.e., limited participation diversity) and participated less frequently (i.e., limited participation intensity) than their typically developing peers; however, companionship, location of participation, and enjoyment level did not differ between the two groups. Children in the DCD group demonstrated significantly worse motor ability as assessed by the MABC-2. Further, a greater proportion of children in the DCD group were in the overweight/obese category compared with their typically developing peers. After accounting for the effects of age and gender, motor ability and weight category explained 7.6% and 5.0% of the variance in participation diversity, respectively, for children with DCD. Children with DCD showed less diverse and less intense out-of-school activity participation than typically developing children. Motor impairment and weight status were independently associated with the lower participation diversity. Interventions aiming at improving participation for children with DCD should target weight control and training in motor proficiency. Further study is needed to identify other factors that may hinder participation in this group of children.

Selective dorsal rhizotomy in Hong Kong: multidimensional outcome measures.

We prospectively case series study evaluated the short-term effectiveness of selective dorsal rhizotomy plus physiotherapy. Twenty children with spastic cerebral palsy, selected for selective dorsal rhizotomy (mean age, 8.57 years; range, 5.96-11.18 years), were assessed before, and 6 and 12 months after, selective dorsal rhizotomy. Main outcome measures included the Modified Ashworth Scale, passive range of joint movement, the Gross Motor Function Measure, the Pediatric Evaluation of Disability Inventory, the Canadian Occupational Performance Measure, and three-dimensional gait analysis. The results confirmed that selective dorsal rhizotomy plus physiotherapy provided a statistically significant reduction of spasticity, functional improvements in mobility and self-care performance, and increased participation in social situations in our study group (85% exhibited normal intelligence, and 90% belonged to Gross Motor Function Classification System levels I-III). The Gross Motor Function Measure proved to be sensitive in documenting motor functional changes, except for children at Gross Motor Function Classification System level I. Instrumental three-dimensional gait analysis with kinematics and kinetics data analysis confirmed gait improvements in children of higher motor function. The Canadian Occupational Performance Measure indicated improvements in social participation.