TRNT1 missense mutations define an autoinflammatory disease characterized by recurrent fever, severe anemia, and b-cell immunodeficiency
نویسندگان
چکیده
Introduction We observed a syndrome characterized by recurrent fever, severe anemia, gastrointestinal symptoms, and a spectrum of immunologic and neurologic symptoms in five children from four unrelated families. Neurologic manifestations ranged from mild developmental delay to nystagmus, spasticity, optic nerve atrophy, and sensorineural hearing loss. Sideroblastic anemia was identified by bone marrow biopsies in two of the children.
منابع مشابه
Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis.
Retinitis pigmentosa (RP) is a highly heterogeneous group of disorders characterized by degeneration of the retinal photoreceptor cells and progressive loss of vision. While hundreds of mutations in more than 100 genes have been reported to cause RP, discovering the causative mutations in many patients remains a significant challenge. Exome sequencing in an individual affected with non-syndromi...
متن کاملTRNT1 deficiency: clinical, biochemical and molecular genetic features
BACKGROUND TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). RESULTS We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting and diarrhoea, global electrolyte imbalance durin...
متن کاملMutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD).
Mutations in genes encoding proteins that are involved in mitochondrial heme synthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis have previously been implicated in the pathogenesis of the congenital sideroblastic anemias (CSAs). We recently described a syndromic form of CSA associated with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Here ...
متن کاملImpaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts
BACKGROUND SIFD (Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay) is a novel form of congenital sideroblastic anemia associated with B-cell immunodeficiency, periodic fevers, and developmental delay caused by mutations in the CCA-adding enzyme TRNT1, but the precise molecular pathophysiology is not known. RESULTS We show that the disease causing mut...
متن کاملBiallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease.
Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one frameshift mutations in one Pakistani and two Turkish families with four affected patients. Patient...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 12 شماره
صفحات -
تاریخ انتشار 2014