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Screening for Fragile X Syndrome Among Filipino Children with Autism Spectrum Disorder

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Abstract

Individuals with autism spectrum disorder present with difficulties in social communication, restricted interests or behaviors and other co-morbidities. About 2 to 10% of cases of autism have a genetic cause, and Fragile X Syndrome (FXS) is reported in 0 to 6.5% of individuals with autism. However, the FXS and premutation prevalence among Filipino children has never been reported. The aim of the study was to establish the presence of FXS or premutation carriers among Filipino children with autism and to describe the phenotypic characteristic of cases identified. Blood was collected from 235 children aged 2–6 years old and diagnosed with autism. Samples were analyzed using PCR methods to amplify CGG repeats in the FMRI gene. The diagnosis of autism was confirmed through the Autism Diagnostic Observation Schedule-2. Additional characteristics were documented from a physical examination, Griffiths Scales of Child Development assessment and a parent-answered questionnaire using the Vineland Adaptive Behavior Scale. Fragile X testing through PCR methods in 235 children with diagnosed autism showed 220 (93.6%) were negative, no full mutations, 1 (0.436%) premutation carrier and 14 (5.95%) cases contained intermediate alleles. The FXS testing was limited to confirmed cases of autism, which is considered a high-risk group and does not provide prevalence for the general Filipino population. Subjects were self-referred or referred by clinicians, which may not represent the Filipino autism population with a bias towards those with means for clinical consultations and ability to travel to the place of testing. Samples were not measured for mosaicism, DNA methylation or AGG interspersion patterns. These may have effects on the CGG repeat expansion and overall presentation of FXS. Findings from a single premutation carrier cannot characterize features distinctly present in Filipinos with the mutation. Nevertheless, these results support the data that the prevalence of FXS in Asian populations may be lower than non-Asian populations. This can contribute to a better understanding of FXS and genetic causes of autism in the Philippines and other Asian populations.

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Abbreviations

ADOS-2:

Autism Diagnostic Observation Schedule

ASD:

Autism spectrum disorder

FMR1:

Fragile X messenger ribonucleoprotein 1

FMRP:

FMR1 protein

FXAND:

Fragile X neuropsychiatric disorders

FXS:

Fragile X Syndrome

FXPOI:

Fragile X-associated Premature Ovarian Insufficiency

FXTAS:

Fragile X-associated tremor/ataxia syndrome

PCR:

Polymerase chain reaction

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Acknowledgments

We are grateful to the families who participated in the research project of the Ateneo Autism Study Group. We also acknowledge the contributions of the following individuals and organizations who provided support to be able to complete the study: CHED-PCARI, Ateneo Center for Research and Innovations, Dr. Eva Cutiongco-dela Paz and the Philippine Genome Center, Dr. Flora Tassone and her laboratory research team and the University of California Davis - MIND Institute, Dr. Feriza Isaguirre with Ms. Maria Catherine B. Otero and Dr. Genevieve Tupas of Davao Medical School Foundation, Inc. and Brokenshire Hospital, Dr. Celina Gellada of West Visayas State University, the Philippine Society for Developmental and Behavioral Pediatrics, past and present clinicians and research assistants of the Ateneo Autism Study Group.

Funding

Funding was provided by Philippine-California Advanced Research Institutes (Grant No. IHITM 2017-024).

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Authors and Affiliations

  1. Ateneo de Manila University School of Medicine and Public Health, Don Eugenio Lopez Sr. Medical Complex, Pasig City, NCR, Philippines

    Angel Belle C. Dy, Lourdes Bernadette S. Tanchanco, Jenica Clarisse Y. Sy & Myla Dominicina Levantino

  2. University of California Davis, MIND Institute, Sacramento, CA, USA

    Randi J. Hagerman

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  1. Angel Belle C. Dy
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  2. Lourdes Bernadette S. Tanchanco
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Contributions

ABCD and LST are co-primary authors who both conducted the clinical assessments of the participants, contributed to the study design, interpreted the data, drafted and reviewed the manuscript. JCS performed the FXS genetic testing, drafted the manuscript, and interpreted the results. MDL performed the sample collection and reviewed the data and manuscript. RJH provided mentorship and contributed to the discussion in the manuscript. All the authors have read and approved the manuscript.

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Correspondence to Angel Belle C. Dy.

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Dy, A.B.C., Tanchanco, L.B.S., Sy, J.C.Y. et al. Screening for Fragile X Syndrome Among Filipino Children with Autism Spectrum Disorder. J Autism Dev Disord 53, 4465–4473 (2023). https://doi.org/10.1007/s10803-022-05707-8

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