الفهرس 
Screening for abnormal spindle like, microcephaly (ASPM) gene mutations in Egyptian families with autosomal recessive primary microcephaly
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Abstract
Autosomal recessive primary microcephaly (MCPH) is a proliferative disorder of brain development that leads to a small size but architecturally normal brain. Although microcephaly is genetically heterogeneous with 14 causative genes but mutations in abnormal spindle-like, microcephaly (ASPM) gene are still the most prevalent cause of the disease. The current study included 37 patients from 30 unrelated families with a clinical diagnosis of MCPH. Screening of ASPM gene mutations was performed by linkage analysis followed by direct sequencing. Thirteen protein-truncating mutations of the ASPM were identified in 15 families (50%). Homozygous ASPM mutations were detected in 11 families while 4 had compound heterozygous mutations. The mutations detected were 8 nonsense, 4 frameshift and 1 splice site. Nine of these mutations were novel and not described elsewhere and two mutations shared similar haplotype suggesting founder effect. The ASPM positive patients had occipitofrontal circumference greater than-3 SD, mild to severe intellectual disability and variable degrees of simplified gyral pattern and frontal lobe hypoplasia. In addition, hypoplasia of corpus callosum, mild cerebellar vermis hypoplasia and relatively small pons were found in 85.7%, 47.6% and 61.9% of patients, respectively. Moreover, one patient had porencephaly and another showed small midline cyst. Epilepsy was documented in two patients. Non-neurologic abnormalities consisted of growth retardation (4 patients), ichthyosis (1 patient) and oculocutaneous albinism (1 patient). This study is the first of its kind to identify the phenotype associated with ASPM mutations in Egyptian patients. Furthermore, it expands the mutation spectrum of ASPM