Zohreh Sharifi - Kawsar Human Genetics-Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
Hanieh Noferesti - Kawsar Human Genetics Research Center (KHGRC), Tehran, Islamic Republic of Iran
Sara Amini - Dr Zeinali’s Medical Genetics Lab, Tehran, Islamic Republic of Iran
Sormeh Pourtavakoli - Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences

Spinal Muscular Atrophy (SMA) is the second most common autosomal recessive genetic disorder with a 1:50 carrier frequency. Deletion /duplication changes in SMN gene are common features in SMA patients. MLPA (Multiplex Ligation-dependent Probe Amplification) is a robust method for investigation of copy number changes because it not only deals with investigating the SMN1 gene but also adjacent genes such as NIPE, GTFH2 and SMN2. Patients with definite diagnosis of SMA were referred to Dr. Zeinali’s Medical Genetics laboratory. Genetic testing of possible deletion/ duplication was performed with MLPA kit (P021, MRC-Holland) based on manufacture protocol.Analysis of data in 80 probands revealed 5 unrelated cases with homozygous deletion of SMN1gene. Further investigation of their parents revealed a heterozygous deletion in one parent and a normal MLPA result in another (i.e. two copy of SMN1 gene). The results were unexpected findings in an autosomal recessive disorder. Paternity and/or maternity were tested and confirmed.Further analysis of the grandparents showed that the parents inherited both deletion/ duplication from one of their parents. So they have 2 copies of SMN1 genes in a chromosome (dup) and no copy on the other one.Due to high carrier frequency of SMA in highly consanguineous population as Iran, co-existence of del/dup must be highly considered. It seems that performing genetic testing of the only in patients is not sufficient and investigation of the parents is also necessary to have reliable results especially for next pregnancies.

Spinal Muscular Atrophy (SMA), Multiplex Ligation-dependent Probe Amplification (MLPA), deletion (del), duplication (dup)