Abstract Primary microcephaly (MCPH) is a genetic disorder in which affected individuals present with a head circumference 3 standard deviations (SDs) below the age- and sex-related mean and is accompanied by mental retardation without further associated malformations. Here we report a patient with sporadic MCPH from Northwest of Iran who was investigated for MCPH1 locus. Clinical examination and karyotype analyses were performed and microsatellite based mapping was done by using flanking and intragenic short tandem repeat (STR) markers for MCPH1 locus. For these markers the affected individual was homozygote and the parents were heterozygote. According to this pattern of allele sharing and also the cytogenetic findings, mutation screening of Microcephalin gene was performed and subsequent sequencing revealed a novel mutation in Microcephalin gene. Keywords: Primary Microcephaly, Mental retardation, Novel mutation, Iran. Introduction Microcephaly is a neurodevelopmental disorder which is characterized with a head circumference 3 standard deviations (SD) below the age-related mean. 1 Microcephaly is divided in two categories: primary microcephaly (MCPH), which is present at birth, and secondary microcephaly, which develops postnatally. 2 The differences between these two groups is that MCPH is usually a static developmental anomaly, whereas secondary microcephaly is a progressive neurodegenerative disorder. 2 In primary microcephaly affected individuals have no neurologic, syndromic, or significantly dysmorphic features but have mild-to-moderate mental retardation (MR). 1 Different causes have been proposed for microcephaly including intrauterine infections, drugs taken during pregnancy, prenatal radiation exposure, maternal phenylketonuria, and birth asphyxia, but these causes are rare with the exception of birth asphyxia. Actually in most of the cases, genetic mechanisms including cytogenetic abnormalities, single-gene disorders, and undetermined etiology syndromes are the major causes of the disease. 3 Autosomal recessive primary microcephaly (MCPH) is a genetically heterogeneous disorder and seven loci Vol. 62, No. 11, November 2012 1244 A novel mutation in MCPH1 gene in an Iranian family with primary microcephaly Miss Masoumeh Hosseini, 1 Seyed Hassan Tonekaboni, 2 Elaheh Papari, 3 Idea Bahman, 4 Farkhondeh Behjati, 5 Kimia Kahrizi, 6 Hossein Najmabadi 7 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), 1,3-7 Neurology Department, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences (SBMU), 2 Tehran, Iran. Corresponding Author: Hossein Najmabadi. Email: hnajm12@ yahoo.com Case Report