Statistics from Altmetric.com
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 …
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.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.