Hepatic fibrinogen storage disease: identification of two novel mutations (p.Asp316Asn, fibrinogen Pisa and p.Gly366Ser, fibrinogen Beograd) impacting on the fibrinogen γ-module.

BACKGROUND: Quantitative fibrinogen deficiencies (hypofibrinogenemia and afibrinogenemia) are rare congenital disorders characterized by low/unmeasurable plasma fibrinogen antigen levels. Their genetic basis is invariably represented by mutations within the fibrinogen genes (FGA, FGB and FGG coding for the Aα, Bß and γ chains). Currently, only four mutations (p.Gly284Arg, p.Arg375Trp, delGVYYQ 346-350, p.Thr314Pro), all affecting the fibrinogen γ chain, have been reported to cause fibrinogen storage disease (FSD), a disorder characterized by protein aggregation, endoplasmic reticulum retention and hypofibrinogenemia. OBJECTIVES: To investigate the genetic basis of FSD in two hypofibrinogenemic patients. METHODS: The mutational screening of the fibrinogen genes was performed by direct DNA sequencing. The impact of identified mutations on fibrinogen structure was investigated by in-silico molecular modeling. Liver histology was evaluated by light microscopy, electron microscopy and immunocytochemistry. RESULTS: Here, we describe two hypofibrinogenemic children with persistent abnormal liver function parameters. Direct sequencing of the coding portion of fibrinogen genes disclosed two novel FGG missense variants (p.Asp316Asn, fibrinogen Pisa; p.Gly366Ser, fibrinogen Beograd), both present in the heterozygous state and affecting residues located in the fibrinogen C-terminal γ-module. Liver sections derived from biopsies of the two patients were examined by immunocytochemical analyses, revealing hepatocyte cytoplasmic inclusions immunoreactive to anti-fibrinogen antibodies. CONCLUSIONS: Our work strongly confirms the clustering of mutations causing FSD in the fibrinogen γ chain between residues 284 and 375. Based on an in-depth structural analysis of all FSD-causing mutations and on their resemblance to mutations leading to serpinopathies, we also comment on a possible mechanism explaining fibrinogen polymerization within hepatocytes.

Dental and periodontal complications of labial and tongue piercing.

Piercing is the practice of puncturing some parts of the body to apply ornamental objects. The presence of oral and perioral piercings are a risk factor for many acute and chronic complications, such as chipping of the dental enamel, periodontal lesions and infection. The aim of this study is to assess the prevalence of lip and tongue piercing complications in the dental and periodontal tissues in a sample of young adults. Twenty-five adult patients were examined (test group: 11 males and 14 females with an average age of 23.4+/-3.6 years) who had had a minimum of one labial or tongue piercing for at least 1 year and were compared with 25 subjects (control group: 11 males - 44 percent, and 14 females - 56 percent) without any lingual or labial piercing. A questionnaire was compiled for each patient and a clinical examination was performed. The following parameters were examined by the same operator: abnormal toothwear, tooth chipping or cracking, clinical attachment loss (CAL), probing pocket depth (PD) and gingival recession (GR, classified by using Miller s classification). The data were analyzed using X2 or Fisher s exact test for small numbers and non-parametric Mann-Whitney or Kruskal-Wallis tests to examine for differences in continuity; the level of significance was p less than 0.05. According to the results found in the present study the prevalence of abnormal tooth wear and tooth chipping was higher in the subjects with labial or lingual piercing. Moreover, patients with tongue or labial piercing exhibited a higher GR in comparison to control subjects without any oral piercing. No differences were observed between the two groups as regards CAL and PD. A significant association between the duration of piercing and dental defects was found in the group of patients with piercings with greater prevalence of tooth and periodontal defects in the group of 13 subjects who had had the piercings for a period less than or equal to 4 years.

Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of immune reconstitution inflammatory syndrome or human papillomavirus (HPV)-related oral diseases were found in this study.

Correlation between otitis media and dental malocclusion in children.

AIM: To determine the possible correlation between otitis media and dental malocclusion in children. METHODS: Fifty subjects (26 males and 24 females; mean age: 7.8 +/- 1 years) were assessed: 25 patients, with otitis media formed the study group, while 25 healthy subjects formed the control group. An otolaryngological examination and dental cast measurements were performed in order to evaluate adenoids, tonsils and dental relationships, respectively. RESULTS: A significant correlation (p<0.05) was found between otitis media and enlargement of adenoids (13 patients, 52% in the study group) and tonsils (11 patients, 44% in the study group). Furthermore, a significant predominance (p<0.05) of posterior crossbite was found in the study group (19 children, 76%), in comparison to the control group (4 children, 16%). No correlation between otitis media and overjet, overbite, Angle Class relationship, or inadequate oral habits were found. CONCLUSIONS: Posterior cross-bite and adenoids-tonsils enlargement are factors significantly associated with otitis media in children.