Eight Novel Mutations in Mlc1 From 18 Iranian Patients With Megalencephalic Leukoencephalopathy With Subcortical Cysts Publisher Pubmed



Kariminejad A¹ ; Rajaee A¹ ; Ashrafi MR² ; Alizadeh H² ; Tonekaboni SH³ ; Malamiri RA⁴ ; Ghofrani M³ ; Karimzadeh P³ ; Mohammadi MM⁵ ; Baghalshooshtari A⁶ ; Bozorgmehr B¹ ; Kariminejad MH¹ ; Postma N⁷ ; Abbink TEM⁷ Show All Authors Show Affiliations
Source: European Journal of Medical Genetics Published:2015

Abstract

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) (MIM #. 604004) is a rare autosomal recessive neurological disorder characterized by macrocephaly, motor and cognitive decline, ataxia, spasticity and occasional seizures. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen white matter of the cerebral hemispheres and subcortical cysts in the anterior temporal and frontoparietal region. Mutations in MLC1(22q13.33) and GLIALCAM have been identified in patients with MLC. Mutations in MLC1 account for approximately 75% of the cases.MLC was suspected in eighteen Iranian patients from sixteen families based on positive clinical findings including macrocephaly beginning in the first year, neurocognitive deterioration, seizure or loss of consciousness after minor head trauma. All except two were born to consanguineous parents. Brain MRI images were compatible with MLC and confirmed the diagnosis. Sequencing of entire coding region of MLC1 was performed for seventeen patients and mutations in MLC1 were detected in all of them. Eight novel mutations and seven previously reported mutations were identified. This report shows that MLC is relatively common in Iranian population, as expected for rare diseases with high inbreeding, with a surprisingly high frequency of novel mutations. © 2014 Elsevier Masson SAS.