ESPE Abstracts (2016) 86 FC9.2

NBAS Mutations, a New Monogenic Cause of DISOPHAL, a New Syndrome with Type 1 Diabetes (T1D)

Anya Rothenbuhlera, Jérôme Maluendab, Cédric Aumontc, Véronique Picardc, Pierre Bougnèresa,b & Judith Melkib


aPediatric Endocrinology, Bicêtre, France; bU1169Inserm, Bicêtre, France; cHematobiology, Bicêtre, France; dCentro Nacional Analisis Genomico, Barcelona, Spain


Background: While non-autoimmune T1D is rare in late childhood, few monogenic causes have yet been identified.

Objective: 1) to identify the genetic basis of the yet unreported disease phenotype associating late childhood antibody-negative T1D, short stature, optic atrophy (OA), Pelger-Huët anomaly (PHA) of leukocytes and recurrent liver cytolysis: the “DISOPHAL” syndrome; 2) to attract comparable cases for further genetic investigation.

Method: Whole-exome sequencing combined with genetic mapping of disease loci.

Results: Compound heterozygous mutations of neuroblastoma amplified sequence (NBAS) were found in three siblings of the same African family who had late childhood antibody-negative insulin-requiring T1D associated with dwarfism, OA, PHA and recurrent episodes of liver cytolysis.

Conclusion: NBAS is a new gene associated with non-autoimmune T1D. NBAS mutations have been reported before in non-diabetic patients with dwarfism, OA and PHA (“SOPH” syndrome) or a separate disorder of recurrent liver failure (“RALF” syndrome). NBAS mutations can induce a wide and heterogeneous clinical spectrum, which showed its complete form in our patients.

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