Majeed Syndrome: Five Cases With Novel Mutations From Unrelated Families in India With a Review of Literature.

OBJECTIVE: Majeed syndrome (MJS) is an autosomal recessive, systemic autoinflammatory disease (SAID) caused by biallelic loss-of-function variants in the LPIN2 gene. It is characterized by early-onset chronic recurrent multifocal osteomyelitis (CRMO), dyserythropoietic anemia, and neutrophilic dermatosis. We analyzed a cohort of uncharacterized Indian patients for pathogenic variants in LPIN2 and other genes associated with SAIDs. METHODS: We performed whole-exome sequencing (WES) for 1 patient and next-generation sequencing (NGS) targeted gene panel for SAIDs in 3 patients. One patient was a referral from neurology after clinical exome sequencing identified a novel variant in LPIN2. We reviewed the literature for all published studies of mutation-positive MJS patients and have summarized their clinical features and disease-causing variants. RESULTS: We describe the largest series of patients with MJS outside of the Middle East. All 5 patients are homozygous for novel, possibly pathogenic variants in the LPIN2 gene. Two of these variants are missense substitutions, and 3 are predicted to alter transcript splicing and create a truncated protein. In addition to the classical features of CRMO and anemia, patients exhibited previously unreported features, including abdominal pain, recurrent diarrhea/ear discharge, and erythema nodosum. CONCLUSION: Patients with MJS may present initially to different specialists, and thus it is important to create awareness in the medical community. In India, consanguinity is a common sociocultural factor in many ethnic communities and an abbreviated NGS gene panel for autoinflammatory diseases should include MJS. The unavailability of interleukin 1 inhibitors in some countries poses a treatment challenge.

Blau arteritis resembling Takayasu disease with a novel NOD2 mutation.

OBJECTIVE: To put forward a new concept--Blau arteritis, a form of large-vessel vasculitis phenotypically related to Takayasu disease but genetically and clinically part of an expanded phenotype of Blau syndrome. METHODS: We provide a clinical description of a new case and summarize previously published cases of arteritis associated with Blau syndrome. Genetic testing was performed by direct sequencing of exon 4 of the NOD2 gene. RESULTS: The case described and those reviewed from the literature demonstrate the emerging phenotype of Takayasu-like arteritis in patients with Blau syndrome. Although most patients described to date depict an otherwise classic Blau syndrome phenotype, the current case was atypical in that the predominant features were arteritic. A novel substitution, G464W, in a highly conserved position near the nucleotide oligomerization domain of the NOD2 protein is also described. CONCLUSION: Blau arteritis can be observed in the context of both typical and atypical (incomplete) Blau syndrome. The associated mutation in the NOD2 gene raises the question of the potential importance of this gene among patients with "primary" forms of Takayasu arteritis.

CINCA Syndrome.

CINCA syndrome is a genetic disorder characterized by early onset of recurrent fever, rash, progressive articular and neurological involvement. We report a 7-year-old girl with CINCA syndrome with an infrequent manifestation of retinal vasculitis and a relative paucity of neurological signs. She had a de novo F309S mutation in exon 3 of CIAS1 gene on chromosome 1. This is the first report of this entity from India.