Impact of Parental Consanguinity on the Frequency of Orofacial Clefts in Jordan.

ABSTRACT: Orofacial clefts (OFCs) are the most common craniofacial congenital anomalies, and its prevalence is highest among Asian populations. The aim of this retrospective case-control study is to evaluate the effect of parental consanguinity on the frequency of OFCs at Jordan University Hospital over a 15-year-period. The study group consists of all patients with OFCs presented to the major tertiary referral center in Jordan during the last 15 years, along with age and gender-matched controls. The authors analyzed the risk of different predictors, including consanguinity, on the development of OFCs, both cleft lip with or without cleft palate (CL/P) and cleft palate only. A total of 332 participants were included in this study, with a mean age of 74.36 (±48.75) months. The authors included 129 (38.9%) OFCs, and 203 (61.1%) controls. The percentage of parental consanguinity among OFCs group was 41.1%, compared to only 24.1% for controls, a difference that was statistically significant (P = 0.001). On logistic regression analysis, the authors found that parental consanguinity is a significant predictor for the occurrence of OFCs (P = 0.007), where people with consanguineous marriage have 2 times higher risk (odds ratio of 0.504, with 95% confidence interval 0.306-0.830) to have offspring with OFCs. Moreover, lower birth weight babies are also significantly more associated with OFCs (P = 0.014), with an odds ratio of 1.819 (95% confidence interval 1.131 2.926). Among the Jordanian population, the authors found that consanguinity and lower birth weight were the only variables significantly associated with the development of OFCs.

Derivation of three human induced pluripotent stem cell lines (JUCTCi014-A, JUCTCi015-A, JUCTCi016-A) from mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue and Wharton's jelly samples.

Mesenchymal stem cells (MSCs) are recognized as a valuable source of cells in clinical treatment and tissue engineering applications. In this study, we created human induced pluripotent stem cells (hiPSCs) from different MSC sources to evaluate the capacity of MSC-derived iPSCs to differentiate into any cell type of the human body and to serve as an alternative source for iPSC generation. Here in, the generated hiPSC lines retained their normal karyotype and showed similar STR-based identities to the parental cells. Reprogrammed cells also showed positive expression of the pluripotency markers and the ability to differentiate into the three germ layers.

Establishment of a human induced pluripotent stem cell line, JUCTCi012-A, from multiple symmetric lipomatosis (MSL) patient carrying a homozygous Arg707Trp (c.2119C > T) mutation in the MFN2 gene.

Induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts collected from a 39-year-old multiple symmetric lipomatosis (MLS) female patient carrying a point mutation in MFN2 gene (c.2119C > T). The resulting iPSCs showed typical embryonic-like morphology, expressed pluripotency stem cell markers, retained the normal karyotype after reprogramming and showed the potential to differentiate into three germ layers. This iPSC line can be used for studying MSL disease mechanisms.

Generation of a human induced pluripotent stem cell (iPSC) line (JUCTCi011-A) from skin fibroblasts of a healthy Jordanian male subject.

Human induced pluripotent stem cell line (JUCTCi011-A) was generated from skin fibroblasts obtained from a 34-year-old healthy male subject from Jordan. The generated iPSCs showed typical embryonic-like characteristics. They retained their normal karyotype similar to their parental dermal fibroblast cells, expressed pluripotency markers and showed a differentiation potential into three germ layers as demonstrated by immunostaining and flow cytometry. This generated cell line can be used in disease modeling studies, to serve as a healthy control line and to help in developing novel therapeutic strategies for patients with hereditary neuromuscular diseases.

Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents.

BACKGROUND: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia, caused by mutations in the APTX gene. The disease is characterized by early-onset cerebellar ataxia, oculomotor apraxia and severe axonal polyneuropathy. The aim of this study was to detect the disease-causing variants in two unrelated consanguineous Jordanian families with cerebellar ataxia using whole exome sequencing (WES), and to correlate the identified mutation(s) with the clinical and cellular phenotypes. METHODS: WES was performed in three affected individuals and segregation analysis of p.W279* APTX candidate variant was performed. Expression levels of APTX were measured in patients' skin fibroblasts and peripheral blood mononuclear cells, followed by western blot analysis in skin fibroblasts. Genotoxicity assay was performed to detect the sensitivity of APTX mutated cells to H2O2, MMC, MMS and etoposide. RESULTS: A recurrent homozygous nonsense variant in APTX gene (c.837G>A, p.W279*) was revealed in all affected individuals. qRT-PCR showed normal APTX levels in peripheral blood and lower levels in fibroblast cells. However, western blot showed the absence of APTX protein in patients' skin fibroblasts. Significant hypersensitivity to H2O2, MMC and etoposide and lack of sensitivity to MMS were noted. CONCLUSIONS: This is the first study to report the identification of a nonsense variant in the APTX gene (c.837G>A; p.W279*) in AOA1 patients within the Jordanian population. This study confirmed the need of WES to assist in the diagnosis of cerebellar ataxia and it emphasizes the importance of studying the pathophysiology of the APTX gene.

Establishment of a human induced pluripotent stem cell (iPSC) line (JUCTCi010-A) from a healthy Jordanian female skin dermal fibroblasts.

Human integration-free induced pluripotent pluripotent stem cells (hiPSCs) were generated from skin fibroblasts obtained from a 27-year-old healthy Jordanian female. The resulting iPSCs expressed the most common pluripotency stem cell markers, they retained the normal karyotype similar to the original fibroblasts and showed the potential to differentiate into three germ layers in vitro. This iPSC line could serve as a wild-type control that can be used in hereditary disease modeling studies and in optimization of different differentiation protocols.

An isolated congenital absence of nasal columella: A case report and review of literature.

INTRODUCTION: The nasal columella is an important aesthetic and functional entity of the midface. Congenital absence of the nasal columella as an isolated anomaly is extremely rare. PRESENTATION OF CASE: We present a case of total congenital aplasia of the nasal columella in a 3-month-old female infant. The deformity was not associated with any other anomalies and with no obvious underlying cause. DISCUSSION: Isolated congenital absence of the nasal columella is an extremely rare anomaly and its etiology is still unknown. Surgical reconstruction of absent nasal columella is challenging as a result of its complex anatomy, and different surgical techniques have been described in the literature to reconstruct the nasal columella with varying advantages and disadvantages. CONCLUSION: The variety in available surgical techniques for the reconstruction of nasal columella necessitates a thorough preoperative evaluation in order to choose the most suitable surgical technique and achieve the best outcome, both functionally and esthetically.

Complete primary pachydermoperiostosis: A case report from Jordan and review of literature.

Complete Primary Pachydermoperiostosis is a rare syndrome that presents with skin and skeletal manifestations. Though diagnosis can be made on the basis of the classic clinical and radiological features, it is often missed due to variable presentations. Therefore, it is important to know about this syndrome to reach correct diagnosis.

An insight into the whole transcriptome profile of four tissue-specific human mesenchymal stem cells.

Aim: Variations in the clinical outcomes using mesenchymal stem cells (MSCs) treatments exist, reflecting different origins and niches. To date, there is no consensus on the best source of MSCs most suitable to treat a specific disease. Methods: Total transcriptome analysis of human MSCs was performed. MSCs were isolated from two adult sources bone marrow, adipose tissue and two perinatal sources umbilical cord and placenta. Results: Each MSCs type possessed a unique expression pattern that reflects an advantage in terms of their potential therapeutic use. Advantages in immune modulation, neurogenesis and other aspects were found. Discussion: This study is a milestone for evidence-based choice of the type of MSCs used in the treatment of diseases.

Giant perianal Seborrheic keratosis: A case report.

INTRODUCTION: Seborrheic keratosis is one of the most common benign epidermal cutaneous lesions encountered by dermatologists and plastic surgeons in their daily practice. PRESENTATION OF THE CASE: A 66-year-old man was presented with a large verrucous mass on the sacrum and perianal area of 10 years duration. After the diagnosis of SK was confirmed, a complete excision of the lesion was done with coverage of the defect with a partial thikness skin graft, with a good outcome. DISCUSSION: Giant Seborrheic keratosis are very rare, and their location on the perianal area is rarer still, with no more than 10 published cases of genital area involvement. CONCLUSION: Giant perianal seborrheic keratoses is a very rare presentation, that may resemble many of the skin disease of that area and should be managed with excision and biopsy to confirm the diagnosis.

Congenital midline sinus of the upper lip: A case report and review of literature.

INTRODUCTION: Congenital pits of the lip are uncommon and may be associated with conditions such as Van der Woude syndrome. Isolated lip pits are extremely rare developmental defects. PRESENTATION OF CASE: A 7 year old Caucasian girl presented to plastic surgery clinic in Jordan University academic hospital complaining of an upper lip pit that has been present since birth. It was associated with a single episode of whitish discharge. On examination, an isolated upper lip midline sinus was found. She is otherwise fit and healthy. Surgical excision was curative with good cosmetic outcome. DISCUSSION: The prevalence of lower lip sinuses has been estimated to be about 0.00001% of the white population. Upper lip sinuses are even more uncommon. To date, there have been several case reports of upper lip sinuses and fistulas. A total of 55 cases was found upon reviewing the English literature. No similar cases were reported in Jordan. Different presentations are mentioned in this review. Several embryologic theories are presented. CONCLUSION: Upper lip sinus formations are rare developmental events, and the pathogenesis of these lesions still needs further evaluation. Simple surgical excision is the treatment of choice.

Skin cancer recognition by using a neuro-fuzzy system.

Skin cancer is the most prevalent cancer in the light-skinned population and it is generally caused by exposure to ultraviolet light. Early detection of skin cancer has the potential to reduce mortality and morbidity. There are many diagnostic technologies and tests to diagnose skin cancer. However many of these tests are extremely complex and subjective and depend heavily on the experience of the clinician. To obviate these problems, image processing techniques, a neural network system (NN) and a fuzzy inference system were used in this study as promising modalities for detection of different types of skin cancer. The accuracy rate of the diagnosis of skin cancer by using the hierarchal neural network was 90.67% while using neuro-fuzzy system yielded a slightly higher rate of accuracy of 91.26% in diagnosis skin cancer type. The sensitivity of NN in diagnosing skin cancer was 95%, while the specificity was 88%. Skin cancer diagnosis by neuro-fuzzy system achieved sensitivity of 98% and a specificity of 89%.

Breast reconstruction by local flaps after conserving surgery for breast cancer: an added asset to oncoplastic techniques.

This study describes and evaluates the results of a proposed simple technique of volume replacement by local flaps to reconstruct the breast after conserving surgery for breast cancer. Twenty-five patients with breast cancer were enrolled in the study between 1998 and 2004. All patients were surgically treated by wide local excision and axillary dissection of level I & II. The primary closure was not feasible because of resulting large defect in proportion to the breast size. The defect was constructed by local flap raised from adjacent skin and subcutaneous tissue with or without glandular breast tissue. Data analyzed includes: age, tumor location, tumor size, histopathology results, operative techniques, complications, long-term oncological events, and cosmetic outcome. The mean follow-up was 48 months. The mean age was 45.3 years. The mean tumor size was 3.1 cm. All tumors had upper outer or upper central location. Fourteen tumors were in left breast. Histopathological analysis had revealed 84% infiltrating ductal carcinoma of no otherwise specified type, 12% medullary type, and 4% tubulo-lobular carcinoma. Additional ductal carcinoma in situ was found in three patients. One patient had focally positive deep margin. One hematoma and one fat necrosis during radiotherapy were documented. During follow-up, one patient developed local recurrence after 4 years and required mastectomy, another patient developed concomitant local recurrence and distant metastasis in the lung and brain after 18 months of the primary treatment and died 1 year later. In this study, 84% of women were satisfied with their cosmetic outcome. This study demonstrated the value of local flaps to reconstruct breast defects after wide local excision of tumors in upper outer or upper central location as simple alternative to latissimus dorsi flap and other volume displacement techniques.