Clinical Case Reports

Biography

Biography: Md Ashraful Islam

Abstract

Rationale: ‘Omenn Syndrome’ is an atypical prototype of Autosomal Recessive form of severe combined immune deficiency (SCID). Patient usually presents with inappropriate exaggerated immunological response featuring dermatitis, hepatosplenomegaly and increased susceptible to infection due to unsecured deficiency of immunoglobulin and T-cell receptor gene recombination machineries. Methods: We report genetic basis of casein ‘Omenn Syndrome’. Results: This is a patient of mixed Asian parents underwent haploidentical paternal stem cell transplantation for a very rare immunological disorder “Omenn Syndrome”. The patient was engrafted and subsequently developed secondary myopathy involving diaphragm as a very rare presentation of Graft Versus Host Disease (GVHD). Fortunately, the patient responded well with steroids winning off of the ventilator. Thereafter, patient has been through several episodes of GVHDs which is being taken care of by the University of Louisville Pediatric Oncology branch. The genetic information of this patient, a younger healthy sibling and parents were investigated for exploring the exact causes of the Omenn Syndrome. We conducted a mutation analysis of Rag1 by PCR amplification of exon 2 and by bi-directional sequencing of the R142X and V779M variants. We have noticed a heterozygous sequence change of C>T in Rag1 resulting in a premature stop codon at Arg142Stoop in mother and two children’s genetic sequence. In addition a heterozygous sequence substitution of G>A in Rag1 gene resulting in V779M mutation observed in father and affected child. We have also determined that the patient is homozygous; father and two children (affected & healthy) are heterozygous for a known functional polymorphism of K820R in Rag1 gene. Conclusions: Rag1 and Rag2 mutation remain the major cause of ‘Omenn Syndrome’ although many other genes can be contributed to the recombination defects. After careful analyzing the genetic information of this patient’s family, we propose for the first time compound heterozygous mutation along with homozygous polymorphism may be the reason for ‘Omenn Syndrome’ at least in this patient. Further clarification of this functional K820R polymorphism will shed light on better understanding of this disease