Genomic analysis of Meckel–Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes

Shaheen, Ranad; Faqeih, Eissa; Alshammari, Muneera; Swaid, Abdulrahman; Al‐Gazali, Lihadh; Mardawi, Elham Al; Ansari, Shinu; Sogaty, Sameera; Seidahmed, Mohammed Zain; Al-Motairi, Muhammed I.; Farra, Chantal; Kurdi, Wesam; Alrasheed, Shatha; Alkuraya, Fowzan S.

doi:10.1038/ejhg.2012.254

Cited by 57 publications

(33 citation statements)

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“…They identified diverse mutations in 10 different genes including 3 novel genes (C5orf42, EVC2, SEC8) . Shaheen et al's study [70] is the largest and most comprehensive genomic study of MKS in Arabs.…”

Section: Meckel Syndromementioning

confidence: 99%

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Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.

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Section: Meckel Syndromementioning

confidence: 99%

“…MKS has also been reported in Saudi Arabia and Tunisia [68,69] . Shaheen et al [70] studied 18 Arab families with MKS using autozygome-guided mutation analysis and exome sequencing. Their study revealed genetic and allelic heterogeneity of this syndrome in Arab families.…”

Section: Meckel Syndromementioning

confidence: 99%

Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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“…These processes may be dependent or independent on its fundamental role in exocytosis. Due to its role in many cellular processes, recent studies have suggested that the mammalian exocyst complex may be implicated in a number of diseases such as kidney disease (Charron et al, ; Fogelgren et al, ), ciliopathy (Fogelgren et al, ; Dixon‐Salazar et al, ; Shaheen et al, ), neuropathogenesis (Bolis et al, ), diabetes (Inoue et al, ; Chen et al, ), and cancers (Sakurai‐Yageta et al, ; Liu et al, ; Ashktorab et al, ; Tanaka et al, , ).…”

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confidence: 99%

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Tanaka

Goto

Iino

2016

Journal Cellular Physiology

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The exocyst complex is a large conserved hetero-oligomeric complex that consists of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 subunits. It has been implicated in the targeting of vesicles for regulated exocytosis in various cell types, and is also important for targeted exocytosis of post-Golgi transport vesicles to the plasma membrane. The exocyst complex is essential for membrane growth, secretion, and function during exocytosis and endocytosis. Moreover, the individual components of the complex are thought to act on specific biological processes, such as cytokinesis, ciliogenesis, apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). As a result, recent studies suggest that the exocyst complex may be involved in several diseases such as kidney disease, neuropathogenesis, diabetes, and cancer. In this review, we focus on the diverse functions and cellular signaling pathways of the exocyst complex in various tumors. J. Cell. Physiol. 232: 939-957, 2017. © 2016 Wiley Periodicals, Inc.

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“…6 Twelve genes are known to cause this disorder when in EVC2 and EXOC4 may also cause MKS. 7 In this study, we show that TMEM231 is the latest gene to be linked to MKS pathogenesis based on pathogenic mutations we identified in two families.…”

Section: Brief Reportmentioning

confidence: 68%

Mutations inTMEM231cause Meckel–Gruber syndrome

et al. 2013

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BackgroundMeckel–Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease.PurposeTo report genetic analysis results in two families in which all known MKS diseases genes have been excluded.MethodsIn two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration.ResultsWe identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state.ConclusionsTMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies.

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Genomic analysis of Meckel–Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes

Cited by 57 publications

References 44 publications

Consanguinity and Dysmorphology in Arabs

Consanguinity and Dysmorphology in Arabs

Diverse Functions and Signal Transduction of the Exocyst Complex in Tumor Cells

Mutations inTMEM231cause Meckel–Gruber syndrome

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