ABSTRACT
BACKGROUND: Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. METHODS: We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5' and 3' untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. RESULTS: We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175-2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. CONCLUSIONS: This study demonstrates that exons 4 and 7 of IRF6 are mutational 'hotspots' in our cohort and that IRF6 mutants-induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high-risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms.
ABSTRACT
Conventional therapy for burns has always produced a nightmarish illness for patients. The lack of the ability to prevent contractures often produces dysfunctional limbs and the ugly scars resulting from severe burns are an ongoing reminder of this lengthy painful illness. This study is to determine the effectiveness of topical heparin in burns management among some patients at the Burns Intensive Care Unit (BICU) of the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Patients for this prospective study were burns victims who were transported to the Accident and Emergency Center of KATH. Complete clerking of the patients and related information were taken. Six patients with ages ranging from 5-35 years, TBSA 5-42% and a combination of 2° and 3° burns were enrolled in the case study. Anatomical locations of the burns included: face, neck, trunk and limbs. Using topical heparin produced smooth skin in two patients: Patients 3 and 5 who reported on Post-burn Day 85 and 116 at the BICU. Five out of the six patients assessed the degree of pain; before treatment with heparin, all five patients stated they were experiencing severe pains, however, three (60.0%) of the patients stated they experienced no pain at all while two (40.0%) were experiencing mild pain after topical heparin application. Heparin was observed to be very effective in the management of burn injuries in the patients studied. It was effective in reduction of pain and prevention of scars and contractures. However, due to the small number of patients and lack of control for the wound healing, a firm recommendation for the use of heparin therapy in burns cannot be made and further studies would be required to establish its use especially in the African population.
