Osteogenesis imperfecta (OI) is a heterogenous group of genetic disorders of bone fragility. OI type V is an autosomal-dominant disease characterized by calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation; the causative mutation involved in this disease has not been discovered yet. Using linkage analysis in a four-generation family and whole-exome sequencing, we identified a heterozygous mutation of c.-14C>T in the 5'-untranslated region of a gene encoding interferon-induced transmembrane protein 5 (IFITM5). It completely cosegregated with the disease in three families and occurred de novo in five simplex individuals. Transfection of wild-type and mutant IFITM5 constructs revealed that the mutation added five amino acids (Met-Ala-Leu-Glu-Pro) to the N terminus of IFITM5. Given that IFITM5 expression and protein localization is restricted to the skeletal tissue and IFITM5 involvement in bone formation, we conclude that this recurrent mutation would have a specific effect on IFITM5 function and thus cause OI type V.

The clinical features and prognostic factor of lymphoma-associated hemophagocytic syndrome (LAHS), diagnosed according to World Health Organization classification, were investigated by reviewing the clinical records of 29 patients between September 1994 and September 2006. Compared with patients with T or natural killer (NK)/T cell LAHS, patients with B cell LAHS were older (p = 0.022), were less likely to exhibit disseminated intravascular coagulation (DIC; p = 0.011), and had less direct involvement of bone marrow (p = 0.03). Clinical response was achieved in 15 (65.2%) and complete remission (CR) was achieved in 4 (17%) of 23 patients who received chemotherapy. Four patients received high-dose chemotherapy and autologous stem cell transplantation (A-SCT), and three of these four patients showed CR. The median survival was 36 days (95%CI, 20.2-51.8). Univariate analysis showed that poor performance status (p = 0.028), T or NK/T cell lymphoma (p = 0.016), presence of jaundice (p = 0.063), the presence of DIC (p = 0.002), and poor clinical response to treatment (p < 0.001) predicted poor overall survival. These data suggest that the clinical features differ significantly between B cell LAHS and T or NK/T cell LAHS. Intensive treatment including high-dose chemotherapy and A-SCT should be investigated.

Ischiospinal dysostosis (ISD) is a polytopic dysostosis characterized by ischial hypoplasia, multiple segmental anomalies of the cervicothoracic spine, hypoplasia of the lumbrosacral spine and occasionally associated with nephroblastomatosis. ISD is similar to, but milder than the lethal/semilethal condition termed diaphanospondylodysostosis (DSD), which is associated with homozygous or compound heterozygous mutations of bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene. Here we report for the first time biallelic BMPER mutations in two patients with ISD, neither of whom had renal abnormalities. Our data supports and further extends the phenotypic variability of BMPER-related skeletal disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0380-0) contains supplementary material, which is available to authorized users.

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Background: Fibrous hamartoma is a key pathologic component of congenital pseudarthrosis of the tibia, a challenging