High-functioning autism spectrum disorder and fragile X syndrome: report of two affected sisters
1 Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
2 INSERM, U955, Créteil, France
3 APHP, Robert Debré Hospital, Department of Child and Adolescent Psychiatry, Paris, France
4 INSERM, U952, Paris, France
5 CNRS, UMR 7224, Paris, France
6 UPMC, Université Paris 06, Paris, France
7 APHP, Department of Genetics, Robert Debré Hospital, Paris, France
8 APHP, Department of Adult Psychiatry, Henri Mondor-Albert Chenevier Hospitals, Créteil, France
9 Faculté de Médecine, Université Paris-Est, Créteil, France
10 CNRS, URA 2182, Paris, France
11 Université Denis Diderot Paris 7, Paris, France
Molecular Autism 2012, 3:5 doi:10.1186/2040-2392-3-5Published: 27 June 2012
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorder (ASD). Men with FXS exhibit ID, often associated with autistics features, whereas women heterozygous for the full mutation are typically less severely affected; about half have a normal or borderline intelligence quotient (IQ). Previous findings have shown a strong association between ID and ASD in both men and women with FXS. We describe here the case of two sisters with ASD and FXS but without ID. One of the sisters presented with high-functioning autism, the other one with pervasive developmental disorder not otherwise specified and low normal IQ.
The methylation status of the mutated FMR1 alleles was examined by Southern blot and methylation-sensitive polymerase chain reaction. The X-chromosome inactivation was determined by analyzing the methylation status of the androgen receptor at Xq12.
Both sisters carried a full mutation in the FMR1 gene, with complete methylation and random X chromosome inactivation. We present the phenotype of the two sisters and other family members.
These findings suggest that autistic behaviors and cognitive impairment can manifest as independent traits in FXS. Mutations in FMR1, known to cause syndromic autism, may also contribute to the etiology of high-functioning, non-syndromic ASD, particularly in women. Thus, screening for FXS in patients with ASD should not be limited to those with comorbid ID.