title: Molecular diagnosis of Fragile X syndrome in subjects with intellectual disability of unknown origin: implications of its prevalence in regional Pakistan.
abstract: Fragile-X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and affects 0.7-3.0% of intellectually compromised population of unknown etiology worldwide. It is mostly caused by repeat expansion mutations in the FMR1 at chromosome Xq27.3. The present study aimed to develop molecular diagnostic tools for a better detection of FXS, to assess implementation of diagnostic protocols in a developing country and to estimate the prevalence of FXS in a cohort of intellectually disabled subjects from Pakistan. From a large pool of individuals with below normal IQ range, 395 subjects with intellectual disability of unknown etiology belonging to different regions of the country were recruited. Conventional-PCR, modified-PCR and Southern blot analysis methods were employed for the detection of CGG repeat polymorphisms in the FMR1 gene. Initial screening with conventional-PCR identified 13 suspected patients. Subsequent investigations through modified PCR and Southern blot analyses confirmed the presence of the FMR1 mutation, suggesting a prevalence of 3.5% and 2.8% (mean 3.3%) among the male and female ID patients, respectively. These diagnostic methods were further customized with the in-house conditions to offer robust screening of referral patients/families for diagnostics and genetic counseling. Prescreening and early diagnosis are crucial for designing a prudent strategy for the management of subjects with ID. Outcome of the study recommends health practitioners for implementation of molecular based FXS diagnosis in routine clinical practice to give a better care for patients similar to the ones included in the study.
authors: Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, 45320 Islamabad, Pakistan.
authors: Madiha
authors: M
authors: Kanwal
authors: Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, 45320 Islamabad, Pakistan.
authors: Saadia
authors: S
authors: Alyas
authors: Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, 45320 Islamabad, Pakistan.
authors: Muhammad
authors: M
authors: Afzal
authors: Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
authors: Atika
authors: A
authors: Mansoor
authors: Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
authors: Rashda
authors: R
authors: Abbasi
authors: M.I.N.D. Institute, University of California Davis, Davis, California, United States of America; Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, California, United States of America.
authors: Flora
authors: F
authors: Tassone
authors: Human Genetics Program, Department of Animal Sciences, Quaid-i-Azam University Islamabad, 45320 Islamabad, Pakistan.
authors: Sajid
authors: S
authors: Malik
authors: Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan.
authors: Kehkashan
authors: K
authors: Mazhar
mesh_terms: D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology*; D007361:Intelligence Tests; D008297:Male; D010154:Pakistan / Q000453:epidemiology; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D063189:Symptom Assessment; D018911:Trinucleotide Repeats; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human