Large homozygous RAB3GAP1 gene microdeletion causes Warburg Micro Syndrome 1

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• 作者：Sylvie Picker-Minh (1) (2) (3)
  Andreas Busche (4)
  Britta Hartmann (4)
  Birgit Spors (5)
  Eva Klopocki (6) (7)
  Christoph H眉bner (1)
  Denise Horn (6)
  Angela M Kaindl (1) (2) (3)
  
  1. Department of Pediatric Neurology ; Charit茅 鈥?Universit盲tsmedizin Berlin ; Campus Virchow-Klinikum ; Augustenburger Platz 1 ; 13353 ; Berlin ; Germany
  2. SPZ Pediatric Neurology ; Charit茅 鈥?Universit盲tsmedizin Berlin ; Campus Virchow-Klinikum ; Augustenburger Platz 1 ; 13353 ; Berlin ; Germany
  3. Institute of Neurobiology and Cell Biology ; Charit茅 鈥?Universit盲tsmedizin Berlin ; Campus Mitte ; Charit茅platz 1 ; 10115 ; Berlin ; Germany
  4. Institute of Human Genetics ; University Medical Center Freiburg ; Breisacher Str. 33 ; 79106 ; Freiburg ; Germany
  5. Department of Pediatric Radiology ; Charit茅 鈥?Universit盲tsmedizin Berlin ; Campus Virchow-Klinikum ; Augustenburger Platz 1 ; 13353 ; Berlin ; Germany
  6. Institute of Medical and Human Genetics ; Charit茅 鈥?Universit盲tsmedizin Berlin ; Campus Virchow-Klinikum ; Augustenburger Platz 1 ; 13353 ; Berlin ; Germany
  7. Current address ; Institute of Human Genetics ; University of W眉rzburg ; Biozentrum Am Hubland ; 97074 ; W眉rzburg ; Germany
  
• 关键词：RAB3GAP1 ; WARBM ; Warburg micro syndrome ; Microcephaly ; Intellectual disability ; Congenital cataract ; Array CGH
• 刊名：Orphanet Journal of Rare Diseases
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：859 KB
• 参考文献：1. Aligianis, IA, Johnson, CA, Gissen, P, Chen, D, Hampshire, D, Hoffmann, K, Maina, EN, Morgan, NV, Tee, L, Morton, J, Ainsworth, JR, Horn, D, Rosser, E, Cole, TRP, Stolte-Dijkstra, I, Fieggen, K, Clayton-Smith, J, M茅garban茅, A, Shield, JP, Newbury-Ecob, R, Dobyns, WB, Graham, JM, Kjaer, KW, Warburg, M, Bond, J, Trembath, RC, Harris, LW, Takai, Y, Mundlos, S, Tannahill, D, Woods, CG, Maher, ER (2005) Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. Nat Genet 37: pp. 221-224 CrossRef
  2. Morris-Rosendahl, DJ, Segel, R, Born, AP, Conrad, C, Loeys, B, Brooks, SS, M眉ller, L, Zeschnigk, C, Botti, C, Rabinowitz, R, Uyanik, G, Crocq, M-A, Kraus, U, Degen, I, Faes, F (2010) New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. Eur J Hum Genet EJHG 18: pp. 1100-1106 CrossRef
  3. Warburg, M, Sj枚, O, Fledelius, HC, Pedersen, SA (1993) Autosomal recessive microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism. Micro syndrome. Am J Dis Child 1960 147: pp. 1309-1312 CrossRef
  4. Bem, D, Yoshimura, S-I, Nunes-Bastos, R, Bond, FC, Bond, FF, Kurian, MA, Rahman, F, Handley, MTW, Hadzhiev, Y, Masood, I, Straatman-Iwanowska, AA, Cullinane, AR, McNeill, A, Pasha, SS, Kirby, GA, Foster, K, Ahmed, Z, Morton, JE, Williams, D, Graham, JM, Dobyns, WB, Burglen, L, Ainsworth, JR, Gissen, P, M眉ller, F, Maher, ER, Barr, FA, Aligianis, IA (2011) Loss-of-function mutations in RAB18 cause Warburg micro syndrome. Am J Hum Genet 88: pp. 499-507 CrossRef
  5. Borck, G, Wunram, H, Steiert, A, Volk, AE, K枚rber, F, Roters, S, Herkenrath, P, Wollnik, B, Morris-Rosendahl, DJ, Kubisch, C (2011) A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome. Hum Genet 129: pp. 45-50 CrossRef
  6. Corbeel, L, Freson, K (2008) Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders. Eur J Pediatr 167: pp. 723-729 CrossRef
  7. Liegel, RP, Handley, MT, Ronchetti, A, Brown, S, Langemeyer, L, Linford, A, Chang, B, Morris-Rosendahl, DJ, Carpanini, S, Posmyk, R, Harthill, V, Sheridan, E, Abdel-Salam, GMH, Terhal, PA, Faravelli, F, Accorsi, P, Giordano, L, Pinelli, L, Hartmann, B, Ebert, AD, Barr, FA, Aligianis, IA, Sidjanin, DJ (2013) Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. Am J Hum Genet 93: pp. 1001-1014 CrossRef
  8. Graham, JM, Hennekam, R, Dobyns, WB, Roeder, E, Busch, D (2004) MICRO syndrome: an entity distinct from COFS syndrome. Am J Med Genet A 128A: pp. 235-245 CrossRef
  9. Handley, MT, Morris-Rosendahl, DJ, Brown, S, Macdonald, F, Hardy, C, Bem, D, Carpanini, SM, Borck, G, Martorell, L, Izzi, C, Faravelli, F, Accorsi, P, Pinelli, L, Basel-Vanagaite, L, Peretz, G, Abdel-Salam, GMH, Zaki, MS, Jansen, A, Mowat, D, Glass, I, Stewart, H, Mancini, G, Lederer, D, Roscioli, T, Giuliano, F, Plomp, AS, Rolfs, A, Graham, JM, Seemanova, E, Poo, P, Garc铆a-Cazorla, A, Edery, P, Jackson, IJ, Maher, ER, Aligianis, IA (2013) Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. Hum Mutat 34: pp. 686-696 CrossRef
  10. M茅garban茅, A, Choueiri, R, Bleik, J, Mezzina, M, Caillaud, C (1999) Microcephaly, microphthalmia, congenital cataract, optic atrophy, short stature, hypotonia, severe psychomotor retardation, and cerebral malformations: a second family with micro syndrome or a new syndrome?. J Med Genet 36: pp. 637-640
  11. Abdel-Salam, GMH, Hassan, NA, Kayed, HF, Aligianis, IA (2007) Phenotypic variability in Micro syndrome: report of new cases. Genet Couns Geneva Switz 18: pp. 423-435
  12. Pavlos, NJ, Xu, J, Riedel, D, Yeoh, JSG, Teitelbaum, SL, Papadimitriou, JM, Jahn, R, Ross, FP, Zheng, MH (2005) Rab3D regulates a novel vesicular trafficking pathway that is required for osteoclastic bone resorption. Mol Cell Biol 25: pp. 5253-5269 CrossRef
  13. Aligianis, IA, Morgan, NV, Mione, M, Johnson, CA, Rosser, E, Hennekam, RC, Adams, G, Trembath, RC, Pilz, DT, Stoodley, N, Moore, AT, Wilson, S, Maher, ER (2006) Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome. Am J Hum Genet 78: pp. 702-707 CrossRef
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• 刊物主题：Medicine/Public Health, general; Pharmacology/Toxicology; Medicinal Chemistry;
• 出版者：BioMed Central
• ISSN：1750-1172

文摘

Warburg micro syndrome (WARBM) is a genetic heterogeneous disease characterized by microcephaly, intellectual disability, brain, ocular, and endocrine anomalies. WARBM1-4 can be caused by biallelic mutations of the RAB3GAP1 (RAB3 GTPase-activating protein 1), RAB3GAP2, RAB18 (RAS-associated protein RAB18), or TBC1D20 (TBC1 domain protein, member 20) gene, respectively. Here, we delineate the so far largest intragenic homozygous RAB3GAP1 microdeletion. Despite the size of the RAB3GAP1 gene deletion, the patient phenotype is mainly consistent with that of other WARBM1 patients, supporting strongly the theory that WARBM1 is caused by a loss of RAB3GAP1 function. We further highlight osteopenia as a feature of WARBM1.