Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is a genetically heterogeneous developmental disorder. The X-linked form of AAS has been ascribed to mutations in the FGD1 gene. However, although AAS may be considered as a relatively frequent clinical diagnosis, mutations have been established in few patients. Genetic heterogeneity and the clinical overlap with a number of other syndromes might explain this discrepancy. In this study, we have conducted a single-strand conformation polymorphism (SSCP) analysis of the entire coding region of FGD1 in 46 AAS patients and identified eight novel mutations, including one insertion, four deletions and three missense mutations (19.56% detection rate). One mutation (528insC) was found in two independent families. The mutations are scattered all along the coding sequence. Phenotypically, all affected males present with the characteristic AAS phenotype. FGD1 mutations were not associated with severe mental retardation. However, neuropsychiatric disorders, mainly behavioural and learning problems in childhood, were observed in five out of 12 mutated individuals. The current study provides further evidence that mutations of FGD1 may cause AAS and expands the spectrum of disease-causing mutations. The importance of considering the neuropsychological phenotype of AAS patients is discussed.

Orrico, A., Galli, L., Cavaliere, M.L., Garavelli, L., Fryns, J., Crushell, E., et al. (2004). Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. EUROPEAN JOURNAL OF HUMAN GENETICS, 12(1), 16-23 [10.1038/sj.ejhg.5201081].

Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients

Orrico, A.;Galli, L.;Sorrentino, V.
2004-01-01

Abstract

Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is a genetically heterogeneous developmental disorder. The X-linked form of AAS has been ascribed to mutations in the FGD1 gene. However, although AAS may be considered as a relatively frequent clinical diagnosis, mutations have been established in few patients. Genetic heterogeneity and the clinical overlap with a number of other syndromes might explain this discrepancy. In this study, we have conducted a single-strand conformation polymorphism (SSCP) analysis of the entire coding region of FGD1 in 46 AAS patients and identified eight novel mutations, including one insertion, four deletions and three missense mutations (19.56% detection rate). One mutation (528insC) was found in two independent families. The mutations are scattered all along the coding sequence. Phenotypically, all affected males present with the characteristic AAS phenotype. FGD1 mutations were not associated with severe mental retardation. However, neuropsychiatric disorders, mainly behavioural and learning problems in childhood, were observed in five out of 12 mutated individuals. The current study provides further evidence that mutations of FGD1 may cause AAS and expands the spectrum of disease-causing mutations. The importance of considering the neuropsychological phenotype of AAS patients is discussed.
Orrico, A., Galli, L., Cavaliere, M.L., Garavelli, L., Fryns, J., Crushell, E., et al. (2004). Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. EUROPEAN JOURNAL OF HUMAN GENETICS, 12(1), 16-23 [10.1038/sj.ejhg.5201081].
File in questo prodotto:
File Dimensione Formato  
Orrico et al 2004 EJHG.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 138.26 kB
Formato Adobe PDF
138.26 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/20712
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo