title: A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE.
abstract: The X-linked condition "Aarskog-Scott syndrome (AAS)" causes a characteristic combination of short stature, facial, genital and skeletal anomalies. Studies elucidated a causative link between AAS and mutations in the FGD1 gene, which encodes a Rho/Rac guanine exchange factor. FGD1 is involved in regulating signaling pathways that control cytoskeleton organization and embryogenesis.
  
  
  
  FGD1 was studied in an Emirati family with two cases of AAS using PCR amplification and direct sequencing of the entire coding region of the gene. Various in silico tools were also used to predict the functional consequences of FGD1 mutations. In the reported family, two brothers harbor a novel hemizygous mutation in FGD1 c.53del (p.Pro18Argfs*106) for which the mother is heterozygous. This frameshift deletion, being close to N-terminus of FGD1, is predicted to shift the reading frame in a way that it translates to 105 erroneous amino acids followed by a premature stop codon at position 106. Full molecular and clinical accounts about the variant are given so as to expand molecular and phenotypical knowledge about this disorder.
  
  
  
  A novel variant in FGD1 was found in an Emirati family with two brothers suffering from AAS. The variant is predicted to be a null mutation, and this is the first report of its kind from the United Arab Emirates.
authors.affiliation: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates. abdul.hamzeh@hmaward.org.ae.
authors.forename: Abdul Rezzak
authors.initials: AR
authors.lastname: Hamzeh
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Fatima
authors.initials: F
authors.lastname: Saif
authors.affiliation: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nair
authors.affiliation: Pediatrics and Neonatology Department, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Asma Jassim
authors.initials: AJ
authors.lastname: Binjab
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Madiha
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates.
authors.forename: Mahmoud Taleb
authors.initials: MT
authors.lastname: Al-Ali
authors.affiliation: Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
authors.forename: Fatma
authors.initials: F
authors.lastname: Bastaki
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004392:Dwarfism / Q000175:diagnosis / Q000235:genetics*; D005145:Face / Q000002:abnormalities*; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D005819:Genetic Markers; D005837:Genitalia, Male / Q000002:abnormalities*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D017384:Sequence Deletion; D014479:United Arab Emirates
chemical_list: C490796:FGD1 protein, human; D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors
keywords: Consanguineous; Emirati; Faciogenital dysplasia; Frameshift deletion; X-linked Aarskog syndrome