A Novel Loss-of-Function Mutation in HOXB1 Associated with Autosomal Recessive Hereditary Congenital Facial Palsy in a Large Iranian Family.

Hereditary congenital facial palsy (HCFP) is a rare congenital cranial dysinnervation disorder, recognisable by non-progressive isolated facial nerve palsy (cranial nerve VII). It is caused by developmental abnormalities of the facial nerve nucleus and its nerve. So far, 4 homozygous mutations have been identified in 5 unrelated families (12 patients) with HCFP worldwide. In this study, a large Iranian consanguineous kindred with 5 members affected by HCFP underwent thorough clinical and genetic evaluation. The candidate gene HOXB1 was screened and analysed by Sanger sequencing. As in previous cases, the most remarkable findings in the affected members of the family were mask-like faces, bilateral facial palsy with variable sensorineural hearing loss, and some dysmorphic features. Direct sequencing of the candidate gene HOXB1 identified a novel homozygous frameshift mutation (c.296_302del; p.Y99Wfs*20) which co-segregated with the disease phenotype within the extended family. Our findings expand the mutational spectrum of HOXB1 involved in HCFP and consolidate the role of the gene in the development of autosomal recessive HCFP. Moreover, the truncating mutation identified in this family leads to a broadly similar presentation and severity observed in previous patients with nonsense and missense mutations. This study characterises and defines the phenotypic features of this rare syndrome in a larger family than has previously been reported.

Serum immune reactivity against ß2-Glycoprotein-I and anti-neutrophil cytoplasmic auto-antibodies by ELI-P-Complex Screening Technology in recurrent miscarriage.

BACKGROUND: A plethora of evidence has shown that circulating auto-antibodies (a-Abs) are critically linked to pregnancy failure. In this study the possible association of serum immune reactivity (IR) against ß2-Glycoprotein-I (ß2GPI) and anti-neutrophil cytoplasmic (ANCA) a-Abs in recurrent miscarriage (RM) was examined. METHODS: This is a case-control study which was carried out in a research and clinical center for infertility, during January to December 2013 on 128 women with RM, matched with 65 women with no history of pregnancy wastage. The participant's sera were collected and serum IR was analyzed against ß2GPI and ANCA a-Abs by ELI-P-Complex screening technology, the assay involved a standard enzyme-linked immunosorbent assay (ELISA). Serum IR of each sample was calculated in conditional units (CU). RESULTS: Elevated serum IR against ß2GPI and decreased serum IR against ANCA a-Abs were detected in a total of 51.5% (N.=66; m=-42 CU) and 24.2% (N.=31; m=-42 CU) patients, respectively. In rare control subjects, serum IR against ß2GPI (3%) and ANCA (1.5%) was observed. The elevated serum IR of ß2GPI was not correlated with the decreased serum IR against ANCA (r=-0.23, P<0.05). Moreover, ß2GPI IR was associated with first trimester miscarriages (P=0.03) and the number of previous miscarriages (P=0.04). CONCLUSIONS: The present study indicates that the risk of RM may be high in women with the prominent serum IR deviations against ß2GPI and ANCA a-Abs. According to the findings and ELI-P-Complex technology principles, it is suggested that the vigorous monitoring of these two a-Abs pre- and during pregnancy may be useful to avoid negative outcomes such as miscarriage.

Chitosan-coated superparamagnetic iron oxide nanoparticles for doxorubicin delivery: synthesis and anticancer effect against human ovarian cancer cells.

Doxorubicin-loaded chitosan-coated superparamagnetic iron oxide nanoparticles (Fe3 O4 ; SPIO-NPs) were prepared by coprecipitation and emulsification cross-linking method and uniform NPs with an average particle size of 82 nm, with high encapsulation efficiencies, were obtained. The drug-loading efficiency of doxorubicin (3.2 mg/mg NPs) showed better results for the chitosan-loaded SPIO-NPs as compared to the bare ones (0.5 mg/mg; p < 0.05). The incubation of A2780 and OVCAR-3 human ovarian cancer cells with doxorubicin-loaded and doxorubicin-loaded chitosan-coated SPIO-NPs, for 24, 48, 72, 96, and 120 h, showed significant IC50 (2.0 ± 0.6 and 7.1 ± 2.7 mm doxorubicin) and IC90 (4.0 ± 9.2 and 10 ± 0.5 mm doxorubicin), respectively, after 96 h of incubation. While, 95% and 98% growth inhibition was seen in A2780 and OVCAR-3 cells after the 96-h exposure to the doxorubicin-chitosan-SPIO-NPs (p < 0.05). A 5-day (120 h) incubation with doxorubicin-chitosan-SPIO-NPs showed that A2780 and OVCAR-3 cells were able to uptake 120 and 110 pg iron/cell, respectively, when treated with doxorubicin-chitosan-SPIO-NPs for 72 h (p < 0.05).