title: Molecular characterization of novel splice site mutation causing protein C deficiency.
abstract: Congenital protein C deficiency is an inherited coagulation disorder associated with an elevated risk of venous thromboembolism. A Saudi Arabian male from a consanguineous family was admitted to neonatal intensive care unit in his first days of life because of transient tachypnea and hematuria. Laboratory investigations determined low platelet and protein C deficiency. Direct sequencing of PROC gene and RNA analysis were performed. Analysis of factor V Leiden (G1691A) and factor II (G20210A) mutations was also done. Novel homozygous splice site mutation c.796+3A>T was detected in the index case and segregation was confirmed in the family. RNA analysis revealed the pathogenicity of the mutation by skipping exon 8 of PROC gene and changing the donor splice site of the exon. Detection of the molecular cause of protein C deficiency reduces life threatening and facilitates inductive carrier testing, prenatal and preimplantation genetic diagnosis for families.
authors.affiliation: aSaudi Diagnostics Laboratory (SDL), Genetics Department, King Faisal Specialist Hospital and Research Centre bPediatric Hematology Division, Pediatrics Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Al-Hamed
authors.forename: Fatma
authors.initials: F
authors.lastname: AlBatniji
authors.forename: Ghadah A
authors.initials: GA
authors.lastname: AlDakheel
authors.forename: Huda
authors.initials: H
authors.lastname: El-Faraidi
authors.forename: Azzah
authors.initials: A
authors.lastname: Al-Zahrani
authors.forename: Fahed
authors.initials: F
authors.lastname: Al-Abbass
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
mesh_terms: D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D003241:Consanguinity; D005091:Exons; D005165:Factor V / Q000235:genetics; D015870:Gene Expression; D006417:Hematuria / Q000097:blood / Q000151:congenital / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008297:Male; D009154:Mutation; D010375:Pedigree; D010976:Platelet Count; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000097:blood / Q000151:congenital / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics; D022821:RNA Splice Sites; D012529:Saudi Arabia; D059246:Tachypnea / Q000097:blood / Q000151:congenital / Q000235:genetics*
chemical_list: D011486:Protein C; D022821:RNA Splice Sites; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin