A Novel Severe Combined Immunodeficiency (SCID) Mutation in Three Mexican Siblings with additional de novo Duchenne Muscular Dystrophy (DMD) mutation

Abstract

RationaleReview a novel common gamma chain (IL2RG) mutation in a consanguineous kindred.MethodsChart review, gene sequencing (Correlagen).ResultsTwo first cousins had 3 children with SCID with c.184T>C (p.cys62Arg) missense mutations in the IL2RG gene (not previously described) with the same father who is unrelated. Two maternal uncles of Pt1 and Pt3 died in infancy.Pt1- Presented at 8 months with failure to thrive, diarrhea, pneumonia and adenoviremia. He received HSCT from an unaffected brother with resultant T, B and NK cell engraftment.Pt2- Presented at birth with neutropenia without identifiable cause on bone marrow biopsy. He received maternal haploidentical HSCT with resultant T and NK cell engraftment but still receives immunoglobulin.Pt3- Presented as healthy newborn. He received a matched unrelated HSCT with T and NK cell engraftment and still receives immunoglobulin. Elevated transaminases without other evidence of graft versus host disease (GVHD) and subtle lower extremity hypotonia led to muscle biopsy. DMD was diagnosed by absence of dystrophin staining and identification of a dystrophin gene mutation non-contiguous with his IL2RG mutation. No other family member shares the DMD mutation. He was started on steroid treatment at 13 months.ConclusionsWe report a kindred with a novel IL2RG mutation and successful HSCT correction. Evaluation for suspected GvHD in one infant revealed a second non-linked spontaneous DMD mutation not previously reported in the literature. The short term impact of pre-HSCT conditioning and prophylaxis and chronic DMD steroid treatment on outcome of both disorders is described. RationaleReview a novel common gamma chain (IL2RG) mutation in a consanguineous kindred. Review a novel common gamma chain (IL2RG) mutation in a consanguineous kindred. MethodsChart review, gene sequencing (Correlagen). Chart review, gene sequencing (Correlagen). ResultsTwo first cousins had 3 children with SCID with c.184T>C (p.cys62Arg) missense mutations in the IL2RG gene (not previously described) with the same father who is unrelated. Two maternal uncles of Pt1 and Pt3 died in infancy.Pt1- Presented at 8 months with failure to thrive, diarrhea, pneumonia and adenoviremia. He received HSCT from an unaffected brother with resultant T, B and NK cell engraftment.Pt2- Presented at birth with neutropenia without identifiable cause on bone marrow biopsy. He received maternal haploidentical HSCT with resultant T and NK cell engraftment but still receives immunoglobulin.Pt3- Presented as healthy newborn. He received a matched unrelated HSCT with T and NK cell engraftment and still receives immunoglobulin. Elevated transaminases without other evidence of graft versus host disease (GVHD) and subtle lower extremity hypotonia led to muscle biopsy. DMD was diagnosed by absence of dystrophin staining and identification of a dystrophin gene mutation non-contiguous with his IL2RG mutation. No other family member shares the DMD mutation. He was started on steroid treatment at 13 months. Two first cousins had 3 children with SCID with c.184T>C (p.cys62Arg) missense mutations in the IL2RG gene (not previously described) with the same father who is unrelated. Two maternal uncles of Pt1 and Pt3 died in infancy. Pt1- Presented at 8 months with failure to thrive, diarrhea, pneumonia and adenoviremia. He received HSCT from an unaffected brother with resultant T, B and NK cell engraftment. Pt2- Presented at birth with neutropenia without identifiable cause on bone marrow biopsy. He received maternal haploidentical HSCT with resultant T and NK cell engraftment but still receives immunoglobulin. Pt3- Presented as healthy newborn. He received a matched unrelated HSCT with T and NK cell engraftment and still receives immunoglobulin. Elevated transaminases without other evidence of graft versus host disease (GVHD) and subtle lower extremity hypotonia led to muscle biopsy. DMD was diagnosed by absence of dystrophin staining and identification of a dystrophin gene mutation non-contiguous with his IL2RG mutation. No other family member shares the DMD mutation. He was started on steroid treatment at 13 months. ConclusionsWe report a kindred with a novel IL2RG mutation and successful HSCT correction. Evaluation for suspected GvHD in one infant revealed a second non-linked spontaneous DMD mutation not previously reported in the literature. The short term impact of pre-HSCT conditioning and prophylaxis and chronic DMD steroid treatment on outcome of both disorders is described. We report a kindred with a novel IL2RG mutation and successful HSCT correction. Evaluation for suspected GvHD in one infant revealed a second non-linked spontaneous DMD mutation not previously reported in the literature. The short term impact of pre-HSCT conditioning and prophylaxis and chronic DMD steroid treatment on outcome of both disorders is described.