KIF5A de novo mutation associated with myoclonic seizures and neonatal onset progressive leukoencephalopathy.

The KIF5A gene (OMIM 602821) encodes a neuron-specific kinesin heavy chain involved in intracellular transport of mitochondria and other cargoes. KIF5A protein comprises the N terminal motor domain, the stalk domain and the C-terminal cargo binding domain. The binding between KIF5A and its cargoes is mediated by kinesin adaptor proteins such as TRAK1 and TRAK2. Numerous missense KIF5A mutations in the motor and stalk domains cause spastic paraplegia type 10 (SPG10, OMIM 604187). Conversely, the role of loss-of-function mutations, especially those affecting the cargo binding domain, is unclear. We describe a novel de novo KIF5A p.Ser974fs/c.2921delC mutation found by whole exome sequencing in a patient with a congenital severe disease characterized by myoclonic seizures and progressive leukoencephalopathy. Since this phenotype differs considerably from the KIF5A/SPG10 disease spectrum we propose that the KIF5A p.Ser974fs and possibly other mutations which lead to truncation of the C-terminal tail of the protein cause a novel disorder. We speculate that the unique effect of the C-terminal truncating KIF5A mutations may result from the previously described complex role of this protein domain in binding of the TRAK2 and possibly other kinesin adaptor protein(s).

[Bronchial asthma: do boys or girls have the highest incidence?]. / Astma oskrzelowa: kto czesciej choruje dziewczeta czy chlopcy?.

The aim of the study was to assess the gender related prevalence of asthma and asthma symptoms in schoolchildren. The survey was performed using standardized ISAAC questionnaire in two age groups: 6-7 yr. (n = 2281; girls 49.7%) and 13-14 yr. (n = 4849; girls 49.8%). It was revealed that in older group the prevalence of ever diagnosed asthma was lower in girls than in boys (2.0% versus 3.3%; odds ratio [OR] = 0.58; p = 0.004). But the prevalence of symptoms: wheeze ever (OR = 1.16; p = 0.056), current wheeze (last 12 mo) (OR = 1.26; p = 0.029), current exercise wheeze (OR = 1.40; p = 0.0008), current night cough (OR = 1.67; p = 0.0001) were higher in girls than in boys. However, in younger group of schoolchildren the prevalence of ever diagnosed asthma and asthma symptoms were higher in boys (5.1% male versus 3.5% female). The girls in comparison to boys revealed lower risk of ever asthma diagnosis (OR = 0.66; p = 0.056) and symptoms: wheeze ever (OR = 0.63; p = 0.0001), current wheeze (OR = 0.69; p = 0.003), current exercise wheeze (OR = 0.59; p = 0.008) and current night cough (OR = 0.70; p = 0.0003).