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Kuwait City, Kuwait

Akizu N.,Howard Hughes Medical Institute | Shembesh N.M.,University of Benghazi | Ben-Omran T.,Hamad Medical Corporation | Bastaki L.,Kuwait Medical Genetics Center | And 18 more authors.
American Journal of Human Genetics | Year: 2013

The corpus callosum is the principal cerebral commissure connecting the right and left hemispheres. The development of the corpus callosum is under tight genetic control, as demonstrated by abnormalities in its development in more than 1,000 genetic syndromes. We recruited more than 25 families in which members affected with corpus callosum hypoplasia (CCH) lacked syndromic features and had consanguineous parents, suggesting recessive causes. Exome sequence analysis identified C12orf57 mutations at the initiator methionine codon in four different families. C12orf57 is ubiquitously expressed and encodes a poorly annotated 126 amino acid protein of unknown function. This protein is without significant paralogs but has been tightly conserved across evolution. Our data suggest that this conserved gene is required for development of the human corpus callosum. © 2013 The American Society of Human Genetics. Source

Marafie M.J.,Kuwait Medical Genetics Center | Al-Mulla F.,Kuwait University
Egyptian Journal of Medical Human Genetics | Year: 2014

Background: Rare autosomal recessive disorders of variable severity are segregating in many highly consanguineous families from the Arab population. One of these deleterious diseases is Senior-Loken syndrome, a hereditary heterogeneous multiorgan disorder, which combines nephronophthisis with retinal dystrophy, leading to blindness and eventually end stage renal failure. This disorder has been reported in many cases worldwide, including two unrelated families from Arabian Gulf countries, which share the gene pool with Kuwait. Case report: Here, we are reporting two children from an Arab family with a novel frameshift mutation found in IQCB1/NPHP5 gene c.1241-1242delTC, predicted to cause protein termination p.Leu414HisfsStop4, and describing the associated clinical features. Conclusion: Identification of this pathogenic mutation helped in confirmation of the clinical diagnosis and in providing a proper pre-marital genetic counselling and testing for a couple embarking on marriage from this highly consanguineous high-risk family. © 2013 . Source

Patrinos G.P.,University of Patras | Patrinos G.P.,University of Melbourne | Al Aama J.,King Abdulaziz University | Al Aqeel A.,King Faisal Specialist Hospital And Research Center | And 11 more authors.
Human Mutation | Year: 2011

Developing countries have significantly contributed to the elucidation of the genetic basis of both common and rare disorders, providing an invaluable resource of cases due to large family sizes, consanguinity, and potential founder effects. Moreover, the recognized depth of genomic variation in indigenous African populations, reflecting the ancient origins of humanity on the African continent, and the effect of selection pressures on the genome, will be valuable in understanding the range of both pathological and nonpathological variations. The involvement of these populations in accurately documenting the extant genetic heterogeneity is more than essential. Developing nations are regarded as key contributors to the Human Variome Project (HVP;), a major effort to systematically collect mutations that contribute to or cause human disease and create a cyber infrastructure to tie databases together. However, biomedical research has not been the primary focus in these countries even though such activities are likely to produce economic and health benefits for all. Here, we propose several recommendations and guidelines to facilitate participation of developing countries in genetic variation data documentation, ensuring an accurate and comprehensive worldwide data collection. We also summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects. © 2010 Wiley-Liss, Inc. Source

Al-Mulla F.,Kuwait University | Marafie M.,Kuwait Medical Genetics Center | Tan T.Z.,National University of Singapore | Thiery J.P.,National University of Singapore | Thiery J.P.,Institute of Molecular and Cell Biology
Journal of Cellular Biochemistry | Year: 2014

In this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence-free survival (RFS) were tested using the Log-rank test in univariate analysis and displayed using Kaplan-Meier curves. Cox proportional-hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal-like, Claudin-low, and Her-2-enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal-like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER- subgroups. RKIP expression had no significant prognostic power within Basal-like, Claudine-low, Luminal B, or Her-2-enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate-poor Luminal A survivors, in both ER+ (P = 0.035) and ER- (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype. J. Cell. Biochem. 115: 488-497, 2014. © 2013 Wiley Periodicals, Inc. Source

Faqeih E.A.,Section of Medical Genetics | Bastaki L.,Kuwait Medical Genetics Center | Rosti R.O.,Howard Hughes Medical Institute | Spencer E.G.,Howard Hughes Medical Institute | And 3 more authors.
American Journal of Medical Genetics, Part A | Year: 2015

Microcephaly-capillary malformation syndrome (MIC-CAP syndrome) is a newly recognized autosomal recessive congenital neurocutaneous central nervous system disorder characterized by severe microcephaly, early-onset seizures, profound psychomotor disability, and multiple cutaneous capillary lesions. In addition, affected patients have variable dysmorphic facial features and hypoplastic distal phalanges. It is distinctively caused by mutations in a newly characterized gene, STAMBP, encoding the deubiquitinating (DUB) isopeptidase that has a key role in cell surface receptor-mediated endocytosis and sorting. Herein, we describe an Arab family of two siblings with classic features of MIC-CAP syndrome that harbor a novel predicted splice mutation in STAMBP, which additionally display previously unreported findings of congenital hypothyroidism and alopecia areata. © 2015 Wiley Periodicals, Inc. Source

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