title: CO-OCCURRENCE OF PRIMARY MICROCEPHALY CAUSED BY A NOVEL HOMOZYGOUS ASPM MUTATION ALONG WITH X-LINKED ICHTHYOSIS IN THE SAME PATIENT.
abstract: Autosomal recessive primary microcephaly is a heterogeneous genetic disorder caused by genes that affect neurogenesis. This form of microcephaly has not been associated with other congenital anomalies. ASPM mutations have been identified as the major cause implicated in autosomal recessive primary microcephaly. X-linked recessive ichthyosis, is an inborn error of steroid sulfatase metabolism characterized by dark and adhesive scaly skin. Here, we examined an Egyptian boy presenting with microcephaly and simplified gyral pattern. Additionally, he had ichthyosis that goes with the X-linked type. Mutation analyses of the ASPM gene for autosomal recessive primary microcephaly and STS gene of X-linked recessive ichthyosis were conducted revealing a co-occurrence of a novel homozygous splice site mutation of ASPM gene (c.2936+1G>A) and a partial deletion of STS spanning from exon 7-10. We propose that the phenotype of our patient results from the combined effects of mutations in both ASPM and STS that account for the neurological signs and skin manifestations, respectively. The association of isolated X-linked recessive ichthyosis and autosomal recessive primary microcephaly has never been reported in the literature. Careful clinical and genetic assessment of patients with atypical clinical phenotypes is crucial for detecting such rare double mutations and thus proper genetic counseling.
authors.forename: M S
authors.initials: MS
authors.lastname: Abdel-Hamid
authors.forename: M F
authors.initials: MF
authors.lastname: Ismail
authors.forename: H A
authors.initials: HA
authors.lastname: Darwish
authors.forename: L K
authors.initials: LK
authors.lastname: Effat
authors.forename: M S
authors.initials: MS
authors.lastname: Zaki
authors.forename: G M H
authors.initials: GM
authors.lastname: Abdel-Salam
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D004534:Egypt; D006720:Homozygote; D006801:Humans; D016114:Ichthyosis, X-Linked / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D043266:Steryl-Sulfatase / Q000235:genetics*
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins; C584039:STS protein, human; D043266:Steryl-Sulfatase