title: A case report: Autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene.
abstract: Autosomal Recessive Primary Microcephaly (MCPH-MIM 251200) is distinguished by congenital decrease in occipito-frontal head circumference (OFC) of at least 2 standard deviations (SD) below population average in addition to non-progressive mental retardation, without any prominent neurological disorder. Mutations in MCPH1, which encodes the protein microcephalin have been detected in this disorder. Here we report a consanguineous Iranian family with 2 children affected with microcephaly. Despite the severe mental retardation observed in the male patient, the female patient had normal intelligent with no delay in motor milestones or speech. A novel splice-acceptor site homozygous mutation has been detected in intron 4 of MCPH1 gene (c.322-2A>T) which results in an RNA processing defect with a 15-nucleotide deletion in exon 5 of the mRNA transcript (r.322_336del15, p.R108_Q112del5). This novel mutation has resulted in different phenotypes in affected male and female patients of this family. The sex-specific variations in gene regulation during brain development may partially explain such difference in phenotypes probably in addition to other mechanisms such as modifier genes.
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Soudeh
authors.initials: S
authors.lastname: Ghafouri-Fard
authors.affiliation: Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Fardaei
authors.affiliation: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Milad
authors.initials: M
authors.lastname: Gholami
authors.affiliation: Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: miryounesi@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Miryounesi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D007492:Iran; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins; D022821:RNA Splice Sites
keywords: MCPH1; Microcephaly; New mutation; Sex-influenced