Do de novo INF2 mutations expand the genetic spectrum of hereditary neuropathy with glomerulopathy?
In exon 2 of INF2, we identified 3 novel mutations that likely affect the protein structure and function. Our findings expand the genetic spectrum of INF2-associated disorders and broaden the associated phenotype with the co-occurrence of intellectual disability and more severe hearing loss than previously reported. De novo INF2 mutations may be more common in patients with CMT disease and FSGS in comparison to FSGS alone. Furthermore, renal dysfunction is more severe and starts earlier in life when associated with CMT disease. Our study confirms that INF2 mutations are a major cause of disease in patients with CMT disease and early signs of nephropathy. Diagnostic screening of INF2 is strongly recommended in isolated patients presenting with CMT disease and FSGS.
We have demonstrated that the intrauterine environment, mainly as mirrored by a low birthweight for gestational age and, independently, neonatal infection diagnosis, is associated with the risk of developing coeliac disease, supporting the idea of a multifactorial aetiology of the disease.