title: Mutation in the SLC29A3 gene: a new cause of a monogenic, autoinflammatory condition.
abstract: Germline mutations in the SLC29A3 gene result in a range of recessive, clinically related syndromes: H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome, Faisalabad histiocytosis, and sinus histiocytosis with massive lymphadenopathy. The main symptoms of these diseases are hyperpigmentation with hypertrichosis, sensorineural deafness, diabetes, short stature, uveitis, and Rosai-Dorfman like histiocytosis. Here, we report the case of an 11-month-old boy with early-onset, recurrent episodes of unprovoked fever lasting 7 to 10 days and associated with pericardial effusion, abdominal pain, diarrhea, and inflammation. Physical examination revealed hyperpigmentation with hypertrichosis, dysmorphic features, and spleen and liver enlargement. Failure to thrive, sensorineural deafness, retarded psychomotor development, and a Rosai-Dorfman like cheek lesion developed subsequently. The febrile episodes did not respond to tumor necrosis factor α antagonists and interleukin-1. Sequencing of the SLC29A3 gene revealed a homozygous missense mutation c.1088G>A (p.Arg363Gln). These observations suggest that a newly identified mutation in the SLC29A3 gene may be associated with an autoinflammatory disorder. Genetic defects in SLC29A3 should be considered in patients with autoinflammatory manifestations, recurrent febrile attacks, and 1 or more of the symptoms found in the broad spectrum of SLC29A3-related disorders (especially hyperpigmentation with hypertrichosis).
authors.affiliation: Department of Pediatric Immunology and Rheumatology (UIH), Hôpital Necker-Enfants Malades, 149 rue de Sèvres, F-75743 Paris, France. isabelle.melki@nck.aphp.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Melki
authors.forename: Karen
authors.initials: K
authors.lastname: Lambot
authors.forename: Laurence
authors.initials: L
authors.lastname: Jonard
authors.forename: Vincent
authors.initials: V
authors.lastname: Couloigner
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
mesh_terms: D005819:Genetic Markers; D056660:Hereditary Autoinflammatory Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology / Q000235:genetics; D006983:Hypertrichosis / Q000209:etiology / Q000235:genetics; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D033703:Nucleoside Transport Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D033703:Nucleoside Transport Proteins; C501424:SLC29A3 protein, human