Al-Aqeel Sewairi syndrome, MIM#605156, a prototype for personalized medicine for the study and prevention of genetic metabolic disorders in Saudi Arabia

Abstract

Aims. Middle Eastern cultures are tribal and heavily consanguineous. Marriage between cousins has been part of the culture for millennia, leading to ‘founder’ effect and a large number of autosomal diseases. In Saudi Arabia, like other Middle Eastern countries, first-cousin marriages account for almost 60–70% of all marriages, leading to uniquely common disorders which are either rare by Western standards or completely unknown. Most of these disorders lead to physical and mental handicap; affected children have poor development and reduced mental capacity. Therefore, accurate diagnosis of the exact molecular defect and prevention is the main aim of our management of these children. Material and Methods. Applying personalized genomics for the diagnosis, prevention and treatment of our patients with genetic metabolic disorders in accordance with our Islamic ethical guidelines is our most important strategy in managing our patients. An example of such an application in Saudi Arabia is the previously described novel autosomal recessive osteolysis/arthritis syndrome, multicentric osteolysis nodulosis with arthritis (MONA) (NOA) (Al-Aqeel Syndrome) (MIM#605156), a distinctive autosomal recessive multicentric osteolysis in Saudi Arabian families with distal arthropathy of the metacarpal, metatarsal and interphalangeal joints, with ultimate progression to the proximal joints with decreased range of movements and deformities with ankylosis and generalized osteopenia. In addition, patients have large, painful to touch palmar and plantar pads; they are also found to have hirsutism and mild dysmorphic facial features including proptosis, a narrow nasal bridge, bulbous nose and micrognathia. Results. The syndrome is caused by inactivating mutations in the MMP2 gene, for which we have established prevention and therapeutic strategy. We have also established with other colleagues the exact genetic defect after establishing the accurate diagnosis and the systematic prevention of genetic disorders by pre-implantation genetic diagnosis with a success in over 160 cases in which the result was the birth of normal children, including patients with Al-Aqeel Sewairi syndrome. We are also establishing stem cell therapy for Genetic Metabolic disorders, with Al-Aqeel Sewairi syndrome as the prototype for such promising modality for treatment of mental and physical handicap in children. These strategies must be done in accordance with our ethical and religious background, with priorities given to the rights of patients and families to know and to make their own decisions as dictated by our Islamic ethics. Conclusion. Personalized medicine includes diagnostic and prognostic approaches, and must include personalized preventive and therapeutic strategies in accordance with our Islamic ethical standards.