ABSTRACT
BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.
Subject(s)
Base Sequence , Dwarfism/genetics , Face/abnormalities , Frameshift Mutation , Genetic Diseases, X-Linked/genetics , Genitalia, Male/abnormalities , Guanine Nucleotide Exchange Factors/genetics , Hand Deformities, Congenital/genetics , Heart Defects, Congenital/genetics , Sequence Deletion , Child , Child, Preschool , Dwarfism/diagnosis , Genetic Diseases, X-Linked/diagnosis , Genetic Markers , Hand Deformities, Congenital/diagnosis , Heart Defects, Congenital/diagnosis , Humans , Male , United Arab EmiratesABSTRACT
OBJECTIVE: To explore the temporal evolution of 25-hydroxyvitamin D [25(OH)D], its epimer, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and minerals in healthy appropriate-for-gestational-age preterms. PATIENTS: A prospective study was undertaken in infants born at 28-32 weeks with monitoring at 1, 3, 5 weeks and term. METHODS: Morning plasma and urine calcium; phosphorus; creatinine; PTH, C-terminal and intact FGF23 (iFGF23) and liquid chromatography-tandem mass spectrometry measurements of 25(OH)D were undertaken. Analyses included regression models. RESULTS: Some 11 infants (5 males) were recruited at a median gestational age of 31.2 weeks (interquartile range: 28.1-31.8). Standard chemistries were normal. No infant was vitamin D deficient; 58% achieved 50 nmol/L with a median intake of 540 IU/day. High concentrations of C-3 epimer were detected. iFGF23 and C-terminal concentrations were persistently elevated (double and ten times adult norms, respectively). Tubular resorption of phosphorus was normal (88%±8%). CONCLUSIONS: Most infants achieved acceptable 25(OH)D3 concentrations. The biologic significance of the elevated FGF23 is unclear.
