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Background  Integrin α3  (ITGA3)  gene mutations are associated with Interstitial Lung disease, Nephrotic syndrome and Epidermolysis bullosa (ILNEB syndrome). To date only six patients are reported: all carried homozygous  ITGA3  mutations and presented a dramatically severe phenotype leading to death before age 2 years, from multi-organ failure due to interstitial lung disease and congenital nephrotic syndrome. The involvement of skin and cutaneous adnexa was variable with sparse hair and nail dysplasia combined or not to skin lesions ranging from skin fragility to epidermolysis bullosa-like blistering.    Results  We report on two siblings of 13 and 9 years born to non-consanguineous healthy parents, who display growth delay, severe pulmonary fibrosis with fatigue, dyspnea on exertion and wheezing, atrophic skin with erythematosus lesions, rare eyelashes/eyebrows and pachyonychia. By exome sequencing, we identified two unreported  ITGA3  missense mutations, c.373G>A (p.(G125R)) in exon 3 and c.821G>A (p.(R274Q)) in exon 6, affecting highly conserved residues in the integrin α3 extracellular N-terminal β-propeller domain. Homology modelling of α3β1 heterodimer fragment, encompassing the mutation sites, showed that G125 plays a pivotal structural role in the β-propeller, while R274 might prevent the interaction between integrin and urokinase complex.    Conclusion  We report a variant of ILNEB syndrome in two siblings differing from the previously reported patients in the lack of nephrotic impairment and survival beyond childhood.  Our siblings are the first reported compound heterozygous for  ITGA3  mutations; this state as well as the hypomorphic nature of their p.(R274Q) mutation likely account for their survival.    Electronic supplementary material  The online version of this article (doi:10.1186/s13023-016-0514-z) contains supplementary material, which is available to authorized users.

Viable phenotype of ILNEB syndrome without nephrotic impairment in siblings heterozygous for unreported integrin alpha3 mutations