Aarskog-Scott syndrome: a novel mutation in the FGD1 gene associated with severe craniofacial dysplasia.
Aarskog syndrome (AAS) is an X-linked human disease that affects the skeletal formation and embryonic morphogenesis and is caused by mutations in the FGD1 gene. Patients typically show distinctive skeletal and genital developmental abnormalities, but a broad spectrum of clinical phenotypes has been observed. We report here on the clinical and molecular analysis of a family that reveals a novel FGD1 mutation in a 9-year-old boy displaying extreme craniofacial dysplasia associated with attention deficit hyperactivity disorder. Sequencing of FGD1 revealed a novel mutation in exon 7 at position c.1468 C > T in the index patient, leading to a stop codon in the highly conserved RhoGEF gene domain. His mother and maternal grandmother were also found to be heterozygous for this FGD1 mutation.


CONCLUSIONS
Our results identify a novel mutation of FDG1 in a family with Aarskog syndrome and underscore the phenotypical variability of this condition.
Department of Otorhinolaryngology, University of Goettingen, Robert Koch-Str. 40, 37075, Goettingen, Germany, christiane.voelter@med.uni-goettingen.de.
Christiane
C
Völter
Ramón
R
Martínez
Rudolf
R
Hagen
Wolfram
W
Kress
D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics; D002648:Child; D004392:Dwarfism / Q000150:complications / Q000235:genetics*; D005145:Face / Q000002:abnormalities*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics*; D005819:Genetic Markers; D005837:Genitalia, Male / Q000002:abnormalities*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000150:complications / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation
C490796:FGD1 protein, human; D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors