Fragile X molecular investigation and genetic counseling of intellectual disability/developmental delay patients in an Indian scenario

ABSTRACT

Background: Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability (ID), is caused by a CGG repeat expansion (full mutation (FM), >200 CGG) at the Fragile X Mental Retardation 1 (FMR1) gene. Early identification of FXS has prognostic significance for affected individuals due to early initiation of interventions. Genetic counseling and family screening can aid parents and at-risk asymptomatic carriers (premutation (PM), 55–200 CGG) in taking proper reproductive decisions.

Methodology: The present study utilizes Triplet Primed-Polymerase Chain Reaction (TP-PCR) methodology for detecting the repeat expansion at FMR1 gene in 233 Indian intellectual disability/developmental delay (ID/DD) patients.

Results: We have identified 18/233 (7.7%) FXS positive cases. Early diagnosis was made in 66.7% cases (<10 years). Extended family screening in 14 affected individuals identified 9 additional FM cases (7 males and 2 females) and 23 carrier PM females, which otherwise could have been missed. Four prenatal diagnoses were also performed, leading to the identification of 1 PM and 1 FM carrier fetus.

Conclusion: A high frequency (7.7%) of FXS among Indian ID/DD subjects obtained in this study depicted the need for more professional recommendations concerning prompt referral for genetic testing, and increased exposure to information about FXS to pediatricians.

KEYWORDS:

• Fragile X syndrome
• molecular analysis
• family screening
• genetic counselling
• TP-PCR

Acknowledgments

Acknowledgments are highly credited to Dr Shubha Phadke; Dr. Inusha Panigrahi, Dr. Kuldeep Singh and their team of consultants for referring ID cases for this study. We are highly grateful to the patients and their family members for providing their consent and participating in this study and to Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh for providing the infrastructure and financial support to Sarita Agarwal for the research work and to Council of Science and Industrial Research (CSIR) – New Delhi for providing fellowship to Deepika DD.

Author Contributions

DDD has done the experimentation and documentation of the results, SA has planned and supervised this study and SM has contributed in compilation of this study and in manuscript preparation.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study is funded by the Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, U.P. (PGI/DIR/RC/307/2016). The fellowship to DDD is provided by the Council of Science and Industrial Research (CSIR) – New Delhi (File no: 09/590/0155/EMR1-2014).