Browsing by Author "Rahman, Fatimah"

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    Mutations in SLC29a3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease
    (Public Library Science, 2010-02) Morgan, Neil V.; Morris, Mark R.; Gleeson, Diane; Straatman-Iwanowska, Anna A.; Davies, Nicholas James; Keenan, Stephen J.; Pasha, Shanaz S.; Rahman, Fatimah; Gentle, Dean C.; Vreeswijk, Maaike P.G.; Devilee, Peter; Knowles, Margaret A.; Ceylaner, Serdar; Trembath, Richard C.; Dalence, Carlos; Kısmet, Erol; Köseoğlu, Vedat; Rossbach, Hans Christoph; Gissen, Paul; Tannahill, David; Mäher, Eamonn Richard; Cangül, Hakan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 8911611600
    The histiocytoses are a heterogeneous group of disorders characterised by an excessive number of histiocytes. In most cases the pathophysiology is unclear and treatment is nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as an autosomal recessively inherited form of histiocytosis with similarities to Rosai-Dorfman disease (RDD) (also known as sinus histiocytosis with massive lymphadenopathy (SHML)). To elucidate the molecular basis of FHC, we performed autozygosity mapping studies in a large consanguineous family and identified a novel locus at chromosome 10q22.1. Mutation analysis of candidate genes within the target interval identified biallelic germline mutations in SLC29A3 in the FHC kindred and in two families reported to have familial RDD. Analysis of SLC29A3 expression during mouse embryogenesis revealed widespread expression by e14.5 with prominent expression in the central nervous system, eye, inner ear, and epithelial tissues including the gastrointestinal tract. SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine. Recently germline mutations in SLC29A3 were also described in two rare autosomal recessive disorders with overlapping phenotypes: (a) H syndrome (MIM 612391) that is characterised by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, heart anomalies, hearing loss, and hypogonadism; and (b) PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus) syndrome. Our findings suggest that a variety of clinical diagnoses (H and PHID syndromes, FHC, and familial RDD) can be included in a new diagnostic category of SLC29A3 spectrum disorder.
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    Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization
    (Nature Portfolio, 2010-04) Cullilane, Andrew Robert; Straatman-Iwanowska, Anna A.; Zaucker, Andreas; Wakabayashi, Yoshiyuki; Bruce, Christopher K.; Luo, Guanmei; Rahman, Fatimah; Gürakan, Figen; Ütine, Gülen Eda; Denecke, Jonas; Vukovic, Jurica; Di Rocco, Maja; Mandel, Hanna; Matthews, Randolph P.; Thomas, Steven G.; Rappoport, Joshua Zachary; Arias, Irwin M.; Wolburg, Hartwig; Knisely, Alexander S.; Kelly, Deirdre Anne K.; Ferenc Müller, Ferenc; Mäher, Eamonn Richard; Gissen, Paul; Özkan, Tanju Başarır; Cangül, Hakan; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 35772174800; 8911611600
    Arthrogryposis, renal dysfunction and cholestasis syndrome (ARC) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells. Mutations in VPS33B account for most cases of ARC. We identified mutations in VIPAR (also called C14ORF133) in individuals with ARC without VPS33B defects. We show that VIPAR forms a functional complex with VPS33B that interacts with RAB11A. Knockdown of vipar in zebrafish resulted in biliary excretion and E-cadherin defects similar to those in individuals with ARC. Vipar-and Vps33b-deficient mouse inner medullary collecting duct (mIMDC-3) cells expressed membrane proteins abnormally and had structural and functional tight junction defects. Abnormal Ceacam5 expression was due to mis-sorting toward lysosomal degradation, but reduced E-cadherin levels were associated with transcriptional downregulation. The VPS33B-VIPAR complex thus has diverse functions in the pathways regulating apical-basolateral polarity in the liver and kidney.