title: Severe combined immunodeficiency caused by a new homozygous RAG1 mutation with progressive encephalopathy.
abstract: We describe an unusual case of severe combined immunodeficiency (SCID) with neutropenia and central nervous system (CNS) manifestations in which a novel RAG1 mutation was identified. A 15-month-old boy presented with failure to thrive, neutropenia and recurrent infections. He was diagnosed with T-B-NK+ SCID. He subsequently developed right partial seizures with ipsilateral hemiparesis and became comatose. Magnetic resonance imaging (MRI) of the brain revealed an inflammatory lesion in the left thalamus which later progressed to diffuse meningo-encephalitis on serial imaging. No CNS infection was documented. Genetic work-up in the child revealed a novel homozygous deleterious mutation in the RAG1 gene (c:2881T>C; p:I794T), for which both parents were heterozygous. He underwent a haploidentical bone marrow transplant without conditioning and died on day +35 with no improvement in his neurological status. The features of neutropenia and progressive encephalopathy could be linked to the novel genetic defect but more data is required to establish this conclusively.
authors: Division of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Sir Ganga Ram Hospital, New Delhi, India.
authors: Nivedita
authors: N
authors: Dhingra
authors: Division of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Sir Ganga Ram Hospital, New Delhi, India. Electronic address: satya_1026@hotmail.com.
authors: Satya Prakash
authors: SP
authors: Yadav
authors: INSERM U768, Hôpital Necker-Enfants Malades, Paris, France.
authors: Jean-Pierre
authors: JP
authors: de Villartay
authors: Centre d'Étude des Déficits Immunitaires, Hôpital Necker-Enfants Malades, APHP, Paris, France.
authors: Capucine
authors: C
authors: Picard
authors: Pediatric Neurology Unit, Department of Pediatrics, Sir Ganga Ram Hospital, New Delhi, India.
authors: R K
authors: RK
authors: Sabharwal
authors: Division of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Sir Ganga Ram Hospital, New Delhi, India.
authors: Veronique
authors: V
authors: Dinand
authors: Department of MRI and CT Scan, Sir Ganga Ram Hospital, New Delhi, India.
authors: Samarjit Singh
authors: SS
authors: Ghuman
authors: Division of Pediatric Hematology-Oncology and Bone Marrow Transplantation, Sir Ganga Ram Hospital, New Delhi, India.
authors: Anupam
authors: A
authors: Sachdeva
mesh_terms: D001483:Base Sequence; D001927:Brain Diseases / Q000150:complications* / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000150:complications* / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein
keywords: Central nervous system; RAG1 mutation; Severe combined immunodeficiency