Long-term follow-up of a patient with 5q31.3 microdeletion syndrome and the smallest de novo 5q31.2q31.3 deletion involving PURA.

Background: Purine-rich element binding protein A (PURA, MIM 600473), is considered the crucial phenocritical gene for an emerging 5q31.3 microdeletion syndrome. To date, at least seven affected individuals with overlapping 5q31.2q31.3 deletions, varying in size from 2.6 to 5 Mb, have been reported sharing neurologic features such as severe developmental delay, neonatal hypotonia, early feeding difficulties, respiratory distress and EEG abnormalities. The recent finding that de novo PURA point mutations are indeed sufficient to cause the severe neurological symptoms also observed in patients with 5q31.2q31.3 deletion further reinforces the gene's causative role in 5q31.3 microdeletion syndrome.

Case Presentation: The present patient, aged 26 years, is the oldest reported individual and carries the smallest de novo 5q31.2q31.3 microdeletion encompassing PURA (360 kb). Her clinical history summarizes the mainly neurodevelopmental phenotype described in children with 5q31.3 microdeletion syndrome. In addition, our patient exhibited a remarkable deterioration of clinical symptoms, starting at the beginning of adolescence, pubertal delay and primary amenorrhea. While epileptic seizures were successfully treated during her life, feeding problems showed a poor outcome, her respiratory problems increased and eventually became severe enough to cause her death.

Conclusion: The clinical and molecular findings reported here provide further evidence that 5q31.3 microdeletion syndrome is a clinically discernible PURA-related disorder and describe the previously unreported natural evolution of the disease in a 26 years old patient.