Microcephaly
Abstract
Microcephaly is a disease associated with reduced brain size and decrease in number of brain cells. Some forms, known as microcephaly primary hereditary (MCPH), are caused by genetic factors. Among them, microcephaly type 5 is the most prevalent and accounts for 50% of cases. It is diagnosed based on reduced head circumference, impairment in intellectual abilities, but presence of normal body size and organization. Patients usually suffer from delayed cognitive development and serious reduction in life quality. The disease is caused by mutations in spindle-like microcephaly associated (ASPA) gene located on chromosome 1 locus q31.3 and production of truncated protein Aspm, which is incapable of mitotic spindle organization. It causes prevalence of asymmetric divisions in neuronal progenitor cells, which is associated with reduced number of brain cells and thus, decrease in organ size. The disease is inherited in autosomal recessive pattern and is characterized by full penetrance, indicating the high importance of timely identification of the mutated allele. Changes in ASPA can be identified during genetic testing, and one of the commonly used tests is Microcephaly Sequencing Panel, which applies massively parallel sequencing for the detection of substitutions, as well as short deletions and duplications.
Microcephaly
Microcephaly is a condition characterized by reduced brain size, when the general organization and architecture of this organ remains normal. It is the basis for its differentiation from neurodevelopmental brain abnormalities characterized by serious organizational defects (Woods and Basto 2014). The primary clinical test for diagnosis of the condition is measurement of head circumference, and microcephaly is evident if this value is more than three standard deviations below the population mean (Zhang 2003). Although this method is clinically effective, it is actually a surrogate tool for identification of brain size (Woods and Basto 2014). At the same time, primary microcephaly is associated with DNA defects, including mutations in ASPM gene (Zhang 2003). It implies that genetic tests could be used for diagnosis or identification of predisposition to the disease (Faheem et al. 2015). Thus, the paper will discuss the main symptoms and complications of primary microcephaly, focus on the associated molecular genetics, and then discuss genetic testing for mutated ASPM gene.
Disease Symptoms
Microcephaly is one of the most common clinical signs in a number of brain disorders with a worldwide prevalence of 2% (Passemard et al. 2016). It can be caused by genetic factors and manifest since birth, or develop in association with neurodegeneration later in life due to exposure to toxic substances (Woods and Basto 2014). In the first case, the disease is referred to as MCPH, while the forms developing due to environmental influences are identified as secondary microcephaly (Faheem et al. 2015). The most common of the primary types is microcephaly primary hereditary type 5 (MCPH5), also known as abnormal spindle-like primary microcephaly (ASPM), as it is associated with mutations in gene ASPA (OMIM 2015). This form of disease will be discussed with respect to the main clinical manifestations. In addition, MCPH5, …
