The IFITM5 gene has recently been found to be mutated in patients with autosomal dominant osteogenesis imperfecta (OI) type V. This form of OI is characterized by distinctive clinical manifestations, including hyperplastic callus formation at the site of fractures, calcification of the interosseous membrane of the forearm, and dislocation of the head of the radius. Notably, in spite of the fact that a considerable number of patients with IFITM5 mutations have been identified, to date all of them have been shown to have the same heterozygous mutation (c.-14C>T). Herein, we describe one patient with a de novo c.119C>T heterozygous mutation in IFITM5, which predicts p.Ser40Leu, and another with the recurrent c.-14C>T transition that was also apparently de novo. While the patient with the p.Ser40Leu mutation had none of the typical signs of OI type V and was diagnosed with limb shortening at prenatal stages, the patient with the c.-14C>T mutation developed hyperplastic calluses and had calcification of the forearm interosseous membrane. This study challenges the lack of allelic and clinical heterogeneity in IFITM5 mutations.

BackgroundOsteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases. Twenty patients had nonrelated parents and were sporadic, and 21 were born to consanguineous relationships.MethodsMutation analysis was performed using a next‐generation sequencing gene panel, homozygosity mapping, and whole exome sequencing (WES).ResultsPatients offspring of nonconsanguineous parents were mostly identified with COL1A1 or COL1A2 heterozygous changes, although there were also a few cases with IFITM5 and WNT1 heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes including CRTAP,FKBP10,LEPRE1,PLOD2,PPIB,SERPINF1,TMEM38B, and WNT1. In addition, two patients born to consanguineous parents were found to have de novo COL1A1 heterozygous mutations demonstrating that causative variants in the collagen I structural genes cannot be overlooked in affected children from consanguineous couples. Further to this, WES analysis in probands lacking mutations in OI genes revealed deleterious variants in SCN9A,NTRK1, and SLC2A2, which are associated with congenital indifference to pain (CIP) and Fanconi–Bickel syndrome (FBS).ConclusionThis work provides useful information for clinical and genetic diagnosis of OI patients with no positive family history of this disease. Our data also indicate that CIP and FBS are conditions to be considered in the differential diagnosis of OI and suggest a positive role of SCN9A and NTRK1 in bone development.

TERCELOI clinical trial addresses fundamental issues concerning the feasibility, security and potential of 5 MSCs infusions in two non immunosuppressed Osteogenesis Imperfecta pediatric patients. This trial allowed us to elucidate the mechanism of action of MSCs therapy, characterized by a pro-osteogenic paracrine response. For that, we studied the protein and miRNA levels in sera from patients (collected before, along and after the cell treatment) besides unraveling the transcriptomic alterations due to those sera presence, and demonstrating their functional capabilities.

This study examined the relationship between caregiver burden and sleep quality in dependent people’s family caregivers. A cross-sectional study was carried out with 201 dependent people’s family caregivers and 92 non-caregivers controls. Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Caregiver Burden Inventory (CBI), and an ad-hoc questionnaire to collect sociodemographic data. Based on CBI scores, subjects were categorized into three groups: family caregivers with high levels of perceived burden, family caregivers with low and medium levels of perceived burden and non-caregiver controls. There were significant differences among the groups in the PSQI total (F = 40.39; p < 0.001), subjective sleep quality (F = 25.55; p < 0.001), sleep latency (F = 16.99; p < 0.001), sleep disturbances (F = 14.90; p < 0.001), use of sleep medications (F = 6.94; p < 0.01) and daytime dysfunction (F = 20.12; p < 0.001). These differences were found only between the caregivers with high levels of perceived burden and the other two groups (p < 0.05). There were also significant differences between the groups in sleep duration (F = 18.34; p < 0.001) and habitual sleep efficiency (F = 24.24; p < 0.001). In these dependent measures, the differences were found in all the pairs examined (p < 0.05). These results suggest that caregiver burden is related to sleep quality, so that caregivers with greater perceived burden have a worse sleep quality.

A randomized controlled trial was carried out with the purpose to determine the effectiveness of EMG-biofeedback in the treatment of chronically constipated elderly patients with dyssynergic defecation as compared to a control condition characterized by information about the bowel functioning and counseling focused on the behavioural mechanisms involved in the defecation. With this purpose, after an initial assessment period (4 weeks), 30 chronically constipated elderly patients with dyssynergic defecation (11 males, 19 females) were randomly assigned to either EMG-biofeedback group (n = 15) or control group (n = 15). The results shown significant improvements in psychophysiological measures (EMG-activity during straining to defecate and anismus index), as well as in clinical variables (frequency of defecations per week, sensation of incomplete evacuation, difficulty evacuation level and perianal pain at defecation) only in the EMG-biofeedback group. The clinical benefits of this behavioural treatment were maintained at the follow-up period 2 months later.