title: Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts.
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.
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran. Electronic address: arianakariminejad@yahoo.com.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Rajaee
authors.affiliation: Pediatrics Centre of Excellence, Department of Pediatric Neurology, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Ashrafi
authors.affiliation: Pediatrics Centre of Excellence, Department of Pediatric Neurology, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Houman
authors.initials: H
authors.lastname: Alizadeh
authors.affiliation: Pediatric Neurology Research Center, SBMU, Tehran, Iran.
authors.forename: Seyed Hasan
authors.initials: SH
authors.lastname: Tonekaboni
authors.affiliation: Department of Paediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Reza Azizi
authors.initials: RA
authors.lastname: Malamiri
authors.affiliation: Pediatric Neurology Research Center, SBMU, Tehran, Iran.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Ghofrani
authors.affiliation: Pediatric Neurology Research Center, SBMU, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Karimzadeh
authors.affiliation: Hazrat Fatemeh Masoumeh Hospital, Qom University of Medical Sciences, Qom, Iran.
authors.forename: Mohsen Molla
authors.initials: MM
authors.lastname: Mohammadi
authors.affiliation: Ahvaz Behzisti Genetic Counseling Center, Ahvaz, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Baghalshooshtari
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Bozorgmehr
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Mohamad Hasan
authors.initials: MH
authors.lastname: Kariminejad
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Postma
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Truus E M
authors.initials: TE
authors.lastname: Abbink
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003560:Cysts / Q000235:genetics*; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D007223:Infant; D007492:Iran; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D055815:Young Adult
chemical_list: C425069:MLC1 protein, human; D008565:Membrane Proteins
keywords: Leukoencephalopathy; MLC1; Megalencephaly; Mutations