Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts.

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits. METHODS: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies. RESULTS: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome. CONCLUSION: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

OBJECTIVE: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. PATIENTS AND METHOD: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. RESULTS: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. CONCLUSION: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

Identification of ASAH1 as a susceptibility gene for familial keloids.

Keloids result from abnormal proliferative scar formation with scar tissue expanding beyond the margin of the original wound and are mostly found in individuals of sub-Saharan African descent. The etiology of keloids has not been resolved but previous studies suggest that keloids are a genetically heterogeneous disorder. Although possible candidate genes have been suggested by genome-wide association studies using common variants, by upregulation in keloids or their involvement in syndromes that include keloid formation, rare coding variants that contribute to susceptibility in non-syndromic keloid formation have not been previously identified. Through analysis of whole-genome data we mapped a locus to chromosome 8p23.3-p21.3 with a statistically significant maximum multipoint LOD score of 4.48. This finding was followed up using exome sequencing and led to the identification of a c.1202T>C (p.(Leu401Pro)) variant in the N-acylsphingosine amidohydrolase (ASAH1) gene that co-segregates with the keloid phenotype in a large Yoruba family. ASAH1 is an acid ceramidase known to be involved in tumor formation by controlling the ratio of ceramide and sphingosine. ASAH1 is also involved in cell proliferation and inflammation, and may affect the development of keloids via multiple mechanisms. Functional studies need to clarify the role of the ASAH1 variant in wound healing.

Quality of life of Nigerians living with human immunodeficiency virus.

INTRODUCTION: Few reports from Nigeria have examined the quality of life (QOL) of people living with HIV/AIDS (PLWHA) despite the fact that Nigeria has the second largest number of PLWHA in the world. This study evaluated the QOL of Nigerians living with HIV/AIDS using the World Health Organization Quality of Life Questionnaire for HIV-Brief Version (WHOQOL-BREF) instrument and assessed the impact of demographic, laboratory and disease-related variables on QOL. METHODS: This cross-sectional study involved 491 consecutive PLWHA aged ≥ 18 years attending the dedicated clinic to PLWHA in South-west Nigeria. RESULTS: The lowest mean QOL scores were recorded in the environment and social domains. Participants aged ≥ 40 years had better QOL in the environment (p = 0.039) and spirituality (p = 0.033) domains and those in relationships had better QOL in the social relationship domain (p = 0.002). Subjects with no or primary education and those who rated their health status as good gave significantly higher ratings in all QOL domains. Participants with AIDS had significant lower QOL in the level of independence domain (p = 0.018) and those with CD4 count ≥ 350 cells /mm3 had better QOL scores in the physical, psychological and level of independence domains. Subjects without tuberculosis co-infection and those on antiretroviral therapy (ART) reported significantly better QOL in the physical, psychological, level of independence and spirituality domains. CONCLUSION: Marital relationship, absence of tuberculosis, CD4 count ≥ 350 cells /mm3 and use of ART positively impacted QOL of our patients.

Recruitment of Yoruba families from Nigeria for genetic research: experience from a multisite keloid study.

BACKGROUND: More involvement of sub-Saharan African countries in biomedical studies, specifically in genetic research, is needed to advance individualized medicine that will benefit non-European populations. Missing infrastructure, cultural and religious beliefs as well as lack of understanding of research benefits can pose a challenge to recruitment. Here we describe recruitment efforts for a large genetic study requiring three-generation pedigrees within the Yoruba homelands of Nigeria. The aim of the study was to identify genes responsible for keloids, a wound healing disorder. We also discuss ethical and logistical considerations that we encountered in preparation for this research endeavor. METHODS: Protocols for this bi-national intercultural study were approved by the Institutional Review Board (IRB) in the US and the ethics committees of the Nigerian institutions for consideration of cultural differences. Principles of community based participatory research were employed throughout the recruitment process. Keloid patients (patient advisors), community leaders, kings/chiefs and medical directors were engaged to assist the research teams with recruitment strategies. Community meetings, church forums, and media outlets (study flyers, radio and TV announcements) were utilized to promote the study in Nigeria. Recruitment of research participants was conducted by trained staff from the local communities. Pedigree structures were re-analyzed on a regular basis as new family members were recruited and recruitment challenges were documented. RESULTS: Total recruitment surpassed 4200 study participants over a 7-year period including 79 families with complete three-generation pedigrees. In 9 families more than 20 family members participated, however, in 5 of these families, we encountered issues with pedigree structure as members from different branches presented inconsistent family histories. These issues were due to the traditional open family structure amongst the Yoruba and by beliefs in voodoo or in juju. In addition, family members living in other parts of the country or abroad complicated timely and complete family recruitment. CONCLUSIONS: Organizational, logistics and ethics challenges can be overcome by additional administrative efforts, good communication, community involvement and education of staff members. However, recruitment challenges due to infrastructural shortcomings or cultural and religious beliefs can lead to significant delays, which may negatively affect study time lines and expectations of funding agencies.

Inhibitory activities of omega-3 Fatty acids and traditional african remedies on keloid fibroblasts.

Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies-boa constrictor oil (BCO) and shea butter-leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fatty acids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fatty acids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fatty acids offer effective and affordable treatment for some keloid patients, especially in the developing world.

Chemical injuries from assaults: An increasing trend in a developing country.

OBJECTIVE: This paper describes chemical injuries, which presented to us and were managed at a burn unit in Nigeria. The purpose of this paper is to highlight the etiologies of these injuries, the extent of the injuries as well as to suggest possible ways to prevent chemical injuries in our environment. MATERIALS AND METHODS: We carried out a retrospective review of chemical burns treated at our center. Our sources of information were the burn unit admission registers, case notes of the patients and operation registers. The results were collated and then analyzed. RESULTS: Twenty eight patients presented with chemical burn injuries during the study period between January 2000 and December 2003, constituting 5.7% of all patients with burns treated within that period. Seventeen (60.7%) of the patients were males while 11 (29.3%) were females with a mean age of 20.6 years. The injuries were sustained from assault in 21 (75%), armed robbery attacks in five (17.8%) and suicide attempts in two (7.1%). The agents were usually unknown. Late presentation was observed in all the patients. Raw eggs, palm oil, gentian violet and engine oil were the substances applied immediately after the injuries. Complications observed included septicemia, respiratory distress, blindness, renal failure, mentosternal contractures, ectropion, axillary contractures, hypertrophic scars, keloids and skin depigmentation. CONCLUSION: Chemical burn injuries are mainly due to assaults in Nigeria and are usually extensive and presented late. Education of the people and penalty for any offender will reduce the current spate of such injuries.

Honey: a reservoir for microorganisms and an inhibitory agent for microbes.

BACKGROUND: Honey is an ancient remedy for the treatment of infected wounds, which has recently been 'rediscovered' by the medical profession. The use to which honey is put in medical care is increasing daily with many authors pointing out its importance and role in wound care. There have been reports that honey contains many microorganisms including bacteria and fungi. OBJECTIVE: The aim of this paper is to highlight the various uses, organisms commonly found in honey, how the organisms arrived in the honey and their effects on wounds and wound care. Would the presence of these organisms not constitute a limiting factor to the use of honey in wound management? This is what this review aims to answer. METHODS: A literature search was done on honey using pubmed, google, local books and journals. Relevant journals were extracted and discussed with emphasis on the antimicrobial properties as well as microbial content of honey and the implications of these. RESULTS: The production of honey as well as the storing process account for the presence of microorganisims. Most of these organisms are said to be in inactive forms as they can hardly survive in honey because of its several properties including hygroscopicity, hyperosmolarity, acidity, peroxide content, antibiotic activities etc. However there is a need for caution in the use of honey in wound management. CONCLUSION: We suggest that wounds to be treated with honey should be investigated i.e with a swab for the microorganisms present on the wound and their sensitivity to the honey before commencing honey treatment. This will help in carefully selecting wounds that might do well with honey treatment not withstanding other properties of honey that aid wound healing.

Management of human bites of the face in Enugu, Nigeria.

BACKGROUND: Human bites of the face present to the surgeon sometimes with a dilemma as to the method and timing of surgery. Often patients present with soft tissue defects as a result of the injury sustained. Reconstruction therefore becomes absolutely necessary to avoid psychosocial complications. OBJECTIVES: The aim of this paper is to review human bites of the face, which presented to the Plastic Surgery Department of the National Orthopaedic Hospital, Enugu, Nigeria over a 10-year period and highlight the epidemiology, presentation, management and its outcome. METHODS: A retrospective review of the cases of human bites of the face that presented within a ten year period was carried out. Sources of information were the case notes and operation registers. Information obtained includes age, gender of the patients as well as that of the assailants and the relationship of the assailants to the patients. Sites of the injuries, management and outcome were also obtained. RESULTS: There were 54 patients seen and treated during the period with the age range 16-54 years (Mean age, 33.8+/-2.3). The male to female ratio was 1:1.6. Various surgical procedures including wedge excision and direct closure (for the lip); midline forehead flap cover, composite auricular graft and nasolabial flaps (for the nose) were carried out. Three of the 9 noses bitten were skin grafted and 3 had primary direct closure. Few complications occurred. CONCLUSION: We conclude that human bites still remain common in our environment. These sometimes need reconstruction due to loss of parts. Minimal debridement with primary closure/reconstruction of human bites of the face; when presented early, gives a good result.