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

Abdul Rezzak Hamzeh,Fatima Saif,Madiha Mohamed,Mahmoud Taleb Al-Ali,Pratibha Nair,Fatma Bastaki,Asma Jassim Binjab

doi:10.1186/s12887-017-0781-4

Abdul Rezzak Hamzeh, Fatima Saif + Show 5 more

Open Access

https://doi.org/10.1186/s12887-017-0781-4

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Abstract

BackgroundThe 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 presentationFGD1 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.ConclusionsA 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.

Highlights

The X-linked condition “Aarskog-Scott syndrome (AAS)” causes a characteristic combination of short stature, facial, genital and skeletal anomalies
A novel variant in FGD1 was found in an Emirati family with two brothers suffering from Aarskog-scott syndrome (AAS)
We present here an Emirati family with two siblings suffering from AAS (Fig. 1d) due to a novel hemizygous mutation in FGD1

Summary

Conclusions

This study reports a novel mutation in FGD1 in an Emirati family with two affected brothers, and these are the first fully characterized cases of Aarskog-Scott Syndrome from the country. Categorizing clinical features in the abovementioned style gives the rather illusive impression of the possibility of reaching a definitive diagnosis through clinical evaluation alone This is not the case because actual patients usually present with combinations of symptoms that appear frequently in numerous other syndromes. The here-reported variant probably leads to total loss of FGD1; phenotypical comparisons between the two mutations do not provide any exclusive common findings especially in relation to behavioral symptoms. This is hardly surprising since FGD1 mutations do not show clear genotypic/phenotypic correlations for mutations affecting the same domain, or even in the cases with the same mutation affecting different patients [9].

Background

Findings