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When extended genetics rescues diagnosis: a patient with CANDLE-like phenotype and de novo mutation in the SAMD9L gene
  1. Amandine Remy1,
  2. Charlotte Borocco2,3,
  3. Guillaume Sarrabay4,
  4. Guilaine Boursier4,
  5. Sylvie Fraitag5,
  6. Benoit Catteau6,
  7. Héloise Reumaux1,
  8. Isabelle Koné-Paut2,3
  1. 1 Pediatric Emergency, Infectious Diseases and Rheumatology Department, CHU Lille, University of Lille, Lille, France
  2. 2 Pediatric Rheumatology Department, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre hospital, AP-HP, university of Paris Saclay, Le Kremlin-Bicêtre, France
  3. 3 University of Paris Saclay, Paris, France
  4. 4 Laboratory of Rare and Autoinflammatory Genetic Diseases and Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), CHU Montpellier, University of Montpellier, Montpellier, France
  5. 5 Pathology Department Paris, France, CHU Necker-Enfants Malades, AP-HP, Paris, France
  6. 6 Dermatology Department, CHU Lille, University of Lille, Lille, France
  1. Correspondence to Dr Amandine Remy, Pediatric Emergency, Infectious Diseases and Rheumatology Department, CHRU de Lille, 59037 Lille, France; amandine_remy_57{at}

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We read with interest Rusmini et al report1 that discussed the application of next-generation sequencing (NGS) in the diagnosis of systemic auto inflammatory diseases (SAID) in 2016. By developing an NGS panel of 10 SAID-associated genes on 50 patients with a known Sanger-identified variant, a third of them were found to carry one or more additional possible effective variants in at least one other gene. Nevertheless, their phenotypic contribution was doubtful, representing the most challenging issue for the use of NGS panels in the daily clinical practice. Herein, we report a striking illustration of the value of extended NGS in patients with unexpected phenotype. We describe the case of a child with prominent inflammatory and cutaneous phenotype, in whom the first NGS panel’s results hypothesised a diagnosis that is analogous to a chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE-like). Despite the identification of a single heterozygous variant in the PSMB8 gene, a second underlying pathogenic variant was suspected given that a genetic digenism is usually frequent in proteasome-associated auto-inflammatory syndromes. But there was more that met the eye: as the patient did not present typical features of CANDLE, genetic investigation was pursued with a whole-exome sequencing revealing a de novo frameshift mutation in the Sterile Alpha Motif Domain–containing protein 9-Like (SAMD9L) gene and leading to the diagnosis of SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD).

The girl was born to unrelated …

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  • Handling editor Josef S Smolen

  • Contributors All autors made substantial contributions to the writing and revising of this letter. Final approval was obtained from each author. Authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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