Wan Azman Wan Sulaiman

Contribution of MSX1 variants to the risk of non-syndromic cleft lip and palate in a Malay population

Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P=0.001, odds ratio=2.241, 95% confidence interval, 1.357–3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition.

Maternal uniparental heterodisomy of chromosome 6 in a boy with an isolated cleft lip and palate.

We describe a chromosome 6 uniparental disomy (UPD6) in a boy, discovered during a screening for the genetic cause of cleft lip and palate. In the medical literature, almost all documented cases of UPD6 are paternal in origin, and only four were maternal. We present here a report of complete maternal chromosome 6 uniparental heterodisomy. Haplotype analysis was performed using highly polymorphic short tandem repeat (STR) markers that span both arms of chromosome 6. Analysis of these markers revealed the presence of two maternal alleles but no paternal allele, indicating an instance of maternal uniparental heterodisomy. Chromosome analysis of peripheral blood lymphocytes confirmed a normal male karyotype. Advanced maternal age at the time of the infants birth and heterodisomy of markers around the centromere favors a meiosis‐I error. No specific phenotype has been reported for maternal UPD6. Therefore, the cleft lip and palate in the present case probably occurred due to other risk factors. This report provides further evidence that maternal UPD6 has no specific clinical consequences and adds to the collective knowledge of this rare chromosomal finding.

Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females

Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.

Reconstruction of large sacral defects following tumour resection: a report of two cases

Sacral tumours often present surgical resection and reconstruction challenges. Wide resections result in large sacral defects and neoadjuvant radiotherapy impairs wound healing. The wounds need to be covered with bulky, well-vascularised, healthy tissues. We present 2 cases where large sacral defects were reconstructed following tumour resection. Both defects were reconstructed with inferiorly based, transpelvic, pedicled vertical rectus abdominis myocutaneous flaps. This is a robust flap and carries a well-vascularised muscle bulk and skin paddle. The donor site is distant from the lesion site and is thus unaffected by both the resection and radiotherapy. This is a useful flap for reconstructing large sacral defects.

The Efficacy of Tualang Honey in Comparison to Silver in Dressing Wounds in Rats

Summary Tualang honey is obtained from large honeycombs produced by Asian bees (Apis dorsata) in gigantic Tualang trees. It has been used traditionally by local communities to treat wounds. However, unlike manuka honey its medicinal uses are not well researched. An open, prospective study into the efficacy of wound healing in full thickness wounds in rats, was designed to compare two honey impregnated dressings with silver-impregnated hydrofibre dressings. A full-thickness wound was created on the dorsum of Sprague-Dawley rats (n=45). Tualang honey impregnated paraffin tulle (P-honey) and tualang honey impregnated hydrofibre dressings (H-honey) were compared with silver-containing hydrofibre dressing (positive control; H-Ag). The wounds were inspected on days 4, 7, 14, 21 and 28. The dressings and wounds were assessed for adherence, ease of removal, fluid accumulation, dryness of skin and exudates, rate of epithelization, healing and wound contraction. Three rats treated with each dressing were sacrificed on the days that wounds were inspected. The wounds and scars were histologically analysed for inflammatory parameters. Tualang honey impregnated dressings were comparable to the commercially available silver impregnated hydrofibre dressing in terms of adherence, ease of removal, fluid accumulation, dryness of surrounding skin and exudates; p > 0.05 for non-parametric Kruskal-Wallis tests and post hoc corrections with a Mann-Whitney test. The rates of wound healing, wound contracture and subsequent histological analysis of inflammatory reaction by each dressing were also comparable. Tualang honey impregnated dressings were as effective as silver impregnated hydrofibre dressings in terms of dressing properties, promotion of wound healing and inflammatory reaction.

Tualang Honey Hydrogel in the Treatment of Split-Skin Graft Donor Sites

Hydrogel is a an established wound dressing. In this prospective single arm study the benefits conferred when tualang honey was added to a hydrogel dressing were investigated with regards to the healing of split skin graft donor sites. Efficacy was evaluated by examining rates of wound healing and pain during the healing of split-skin graft donor using Tualang Honey Hydrogel. Patients who underwent split skin grafting were screened and those who met the inclusion criteria were recruited from the patient population in Hospital Universiti Sains Malaysia (HUSM) over a period of 18 months. Individual informed consent was obtained from each patient. Thirty-five patients received Honey Hydrogel dressing applied to their split skin graft donor sites. All donor sites were inspected on the 10, 15 and 20th post-operative day. Complete healing between post-operative day 10 and post-operative day 15 was observed, with minimal pain, discomfort and pruritus. Honey Hydrogel may be effective in the treatment of split-skin graft donor sites, warranting further studies to compare it with existing dressing materials.

Contribution of variants in and near the IRF6 gene to the risk of nonsyndromic cleft lip with or without cleft palate in a Malay population.

Several studies have shown evidence for the contribution of interferon regulatory factor 6 (IRF6) variants to the risk of nonsyndromic oral clefts in Asians; however, this has not included the Malay population. The current study attempts to address this research gap using allele and haplotype transmission disequilibrium analyses. The results showed a strong transmission distortion for multiple haplotypes to patients with nonsyndromic cleft lip with or without cleft palate. Haplotypes carrying the 243 bp allele of D1S2136 and common alleles at the rs861019 and rs2235371 were over‐transmitted to patients. By contrast, haplotypes consisting of the 251 bp allele of D1S2136 and the rare allele at rs2235371 were more under‐transmitted. Furthermore, several variants and haplotypes showed excess maternal transmission, but none of them attained statistical significance in maternal relative risk analyses. In contrast, a significant child genotype effect was observed for several haplotypes, indicating fetal genotype could be the major genetic contribution rather than maternal genotype. The present study therefore further supports a role for IRF6 variants in clefting in this Southeast Asian population. Overall, Asian genetic backgrounds are most likely more susceptible to the haploinsufficiency of IRF6 variants. These variants may contribute to the condition either themselves, or they may be in linkage disequilibrium with other casual variants.

Discovery of candidate genes for nonsyndromic cleft lip palate through genome-wide linkage analysis of large extended families in the Malay population

BackgroundNonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population.ResultsA significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1.ConclusionsWe have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.

Contribution of 6p24 to Non-syndromic Cleft Lip and Palate in a Malay Population Association of Variants in OFC1

Non-syndromic cleft lip, with or without cleft palate, is a heterogeneous, complex disease with a high incidence in the Asian population. Several association studies have been done on cleft candidate genes, but no reports have been published thus far on the Orofacial Cleft 1 (OFC1) genomic region in an Asian population. This study investigated the association between the OFC1 genomic region and non-syndromic cleft lip with or without cleft palate in 90 Malay father–mother–offspring trios. Results showed a preferential over-transmission of a 101-bp allele of marker D6S470 in the allele- and haplotype-based transmission disequilibrium test (TDT), as well as an excess of maternal transmission. However, no significant p-value was found for a maternal genotype effect in a log-linear model, although single and double doses of the 101-bp allele showed a slightly increased cleft risk (RR = 1.37, 95% CI, 0.527-3.4, p-value = 0.516). Carrying two copies of the 101-bp allele was significantly associated with an increased cleft risk (RR = 2.53, 95% CI, 1.06-6.12, p-value = 0.035). In conclusion, we report evidence of the contribution of the OFC1 genomic region to the etiology of clefts in a Malay population.

Inconspicuous Nasoethmoidal Encephalocele Might Be Wrongly Diagnosed

Dear Editor-in-Chief, We have read the paper of Song et al. [1] on frontonasal dysplasia deformity. It was an interesting discussion of an image that depicts a boy with a nose deformity, and it was reported that no basal encephalocele was observed. We would like to point out that we had a similar case of a girl with the same nose deformity. As in the report by Song et al., our patient also presented with mild hypertelorism, a broad nasal root and a bifid nasal tip (Fig. 1). The defect at the nasal dorsum had never increased in size and was not cystic. Her parents were anxious about the cosmetic appearance of their child and requested an early excision of the nasal defect and rhinoplasty. Fig. 1 (A, B) A 6 months old, Malay girl with features of nasoethmoidal encephalomeningocele, including telecanthus, broadening of the nasal root with irregular nasal dorsal skin and lack of a nasal tip. Intraoperatively, we noted a very small stalk passing between the nasal bone and the upper lateral cartilage (Fig. 2A, B). The stalk was faintly seen on the magnetic resonance imaging due to its very small size. This small stalk passed from an internal location between the frontal and ethmoidal bone to an external location between the nasal bone and the upper lateral cartilage (Fig. 2C). Fig. 2 (A, B) Stalk of the lesion passing in between the nasal bone and upper lateral cartilage