The 15q13.3 deletion is significantly associated with neurodevelopmental diseases, and is observed in approximately 1 in 3000 live births. The primary 15q13.3 deletion spans 6 genes of interest: FAN1, MTMR10, TRPM1, KLF13, OTUD7A, and CHRNA7 (right figure). Some affected individuals carry partial deletions that only affect OTUD7A and CHRNA7.
A wide array of clinical features have been associated with the 1q21.1 deletion. Individuals with the deletion are likely to exhibit intellectual disability, developmental delay, speech delay and behavioral problems such as ADHD and mood disorders. Epilepsy is also strongly associated with the deletion, as the deletion is responsible for >1% of generalized epilepsy cases (particularly absence and myoclonic seizures). A subset of 15q13.3 deletion carriers are further diagnosed with autism spectrum disorders, schizophrenia, and (rarely) cardiac defects. However, individuals with the deletion do not share the same sets of symptoms, which indicates that this deletion is non-syndromic.
Individuals with the deletion have a sensitized genomic background rendering them vulnerable to multiple neurodevelopmental disorders such as intellectual disability, autism, and epilepsy. We are currently studying the 15q13.3 deletion as a paradigm to understand the complex genetics of developmental disorders. We hypothesize that genetic variants near or within the CNV interval and/or at a second site elsewhere in the genome contribute to the phenotypic outcome of disorders association with the deletion. Because the 15q13.3 deletion is inherited from parents in >80% of cases, assessing family history is essential to understanding the disease.
Most genomic deletions are the result of non-allelic homologous recombination (NAHR) between large (larger than 10kb) and highly similar sequences of DNA called segmental duplications. Several chromosomes are enriched in these types of DNA sequences, including the long arm of chromsome 15 (15q). This leads to a higher frequency of these rearrangements and therefore genomic disorders associated with this variation.
Study of the 15q13.3 deletion continues to be promising in understanding the variable clinical features associated with the disorder, and will lay a foundation to provide better treatment methods to patients in the years to come.
We are currently recruiting individuals with the 15q13.3 deletion and their family members for this study, and invite you to participate if your child or loved one has been affected by the deletion. The following link leads to an initial questionnaire, which we will use to obtain some preliminary information about you and your family members who carry the 15q13.3 deletion.
We estimate that the survey will take approximately 15 minutes to complete. We note that participation in this questionnaire is completely voluntary. All answers will be kept strictly confidential, and protected to the maximum extent as required by law.
After you complete the questionnaire, we will contact you directly with further information on our study. Your participation in this study will be very important in understanding the connections between genetic variants and the symptoms identified in individuals carrying the 15q13.3 deletion.
Link to 15q13.3 deletion questionnaire