Dataset Information

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.

SUBMITTER: Hamzeh AR

PROVIDER: S-EPMC5248450 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE.

Hamzeh Abdul Rezzak AR Saif Fatima F Nair Pratibha P Binjab Asma Jassim AJ Mohamed Madiha M Al-Ali Mahmoud Taleb MT Bastaki Fatma F

BMC pediatrics 20170119 1

<h4>Background</h4>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.<h4>Case presentation</h4>FGD1 was studied in an Emirati family with two cases of AAS using PCR a ...[more]

PMID: 28103835

Similar Datasets

Project description:Background Aarskog–Scott syndrome, a rare X-linked genetic disorder, is identified by combined clinical manifestations of short stature, facial, skeletal, and genital anomalies. Annually, two or three new cases are diagnosed with Aarskog–Scott syndrome, which is associated with FGD1 variants. However, there is no specific treatment for Aarskog–Scott syndrome due to its unclear mechanism. Methods Clinical data were collected when the patient first visited the hospital. Trio whole-exome sequencing and Sanger sequencing were performed for the genetic cause of disease. To evaluate the pathogenicity of the variants in vitro, stable cell lines were constructed using lentivirus infection in 143B cell. Furthermore, Western blot was used to verify the expression of signaling pathway-related proteins, and the transcription levels of osteogenic-related genes were verified by luciferase reporter gene assay. Results A 7-year-old boy was manifested with facial abnormalities, intellectual disability, and short stature (−3.98 SDS) while the growth hormone level of stimulation test was normal. Trio whole-exome sequencing and Sanger sequencing identified a variant (c.1270A>G, p.Asn424Asp) in FGD1 gene. The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein. In vitro study showed that the Asn424Asp variant significantly decreased the transcription levels of OCN, COL1A1, and ALP activity, and it activated the phosphorylation of JNK1. Conclusion Molecular biological mechanisms between abnormal expression of FGD1and Aarskog–Scott syndrome remain poorly understood. In our study, c.1270A>G variant of FGD1 resulted in Aarskog–Scott syndrome, and the analysis of pathogenicity supports the deleterious effect of the variant. Furthermore, we demonstrated the weakened affinity of the mutant FGD1 and CDC42. Decreased expression of osteogenic-related gene and abnormal activation of JNK1 were also shown in this work.

Dataset Information

A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE.

Publications

A novel, putatively null, FGD1 variant leading to Aarskog-Scott syndrome in a family from UAE.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets