RAC1 Missense Mutations in Developmental Disorders with Diverse Phenotypes

American Journal of Human Genetics

Volumn 101, Issue 3, 2017, Pages 466-477

  Reijnders, Margot R F ^a   Ansor, Nurhuda M ^b,c   Kousi, Maria ^d   Yue, Wyatt W ^e   Tan, Perciliz L ^d   Clarkson, Katie ^f   Clayton Smith, Jill ^b,g   Corning, Ken ^f   Jones, Julie R ^f   Lam, Wayne W K ^h   Mancini, Grazia M S ⁱ   Marcelis, Carlo ^a   Mohammed, Shehla ^j   Pfundt, Rolph ^a   Roifman, Maian ^k,l   Cohn, Ronald ^l   Chitayat, David ^k,l   Millard, Tom H ^b   Katsanis, Nicholas ^d   Brunner, Han G ^a,m   Banka, Siddharth ^b,g   more..

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c ADVANCED MEDICAL AND DENTAL INSTITUTE   (Malaysia)

^d DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f GREENWOOD GENETIC CENTER   (United States)

^g ST MARY S HOSPITAL   (United Kingdom)

^h WESTERN GENERAL HOSPITAL   (United Kingdom)

ⁱ ERASMUS MEDICAL CENTER   (Netherlands)

^j GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^k MOUNT SINAI HOSPITAL   (Canada)

^l HOSPITAL FOR SICK CHILDREN   (Canada)

^m MAASTRICHT UNIVERSITY   (Netherlands)

more..

Author keywords

cerebellar abnormalities; developmental disorders; HACE1; intellectual disability; macrocephaly; microcephaly; neuronal proliferation; RAC1; Rho GTPase; TRIO

Indexed keywords

RAC1 PROTEIN; RAC1 PROTEIN, HUMAN;

ADOLESCENT; AMINO ACID SUBSTITUTION; AMINO TERMINAL SEQUENCE; ARTICLE; BRAIN MALFORMATION; CELL PROLIFERATION; CHILD; CLINICAL ARTICLE; COMPUTER MODEL; CONTROLLED STUDY; DEVELOPMENTAL DELAY; DEVELOPMENTAL DISORDER; DISEASE SEVERITY; EMBRYO; FACE DYSMORPHIA; GENE; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; GENETIC VARIATION; HACE1 GENE; HEAD CIRCUMFERENCE; HUMAN; IN VIVO STUDY; INFANT; MACROCEPHALY; MALE; MICROCEPHALY; MISSENSE MUTATION; NERVE CELL; NERVE CELL DIFFERENTIATION; NONHUMAN; PHENOTYPE; PHENOTYPIC VARIATION; PRESCHOOL CHILD; PRIORITY JOURNAL; RAC1 GENE; SCHOOL CHILD; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; TRIO GENE; ZEBRA FISH; AMINO ACID SEQUENCE; ANIMAL; BRAIN DISEASE; FEMALE; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; MOUSE; NONMAMMALIAN EMBRYO; PATHOLOGY; PEDIGREE;

ADOLESCENT; AMINO ACID SEQUENCE; ANIMALS; BRAIN DISEASES; CHILD; CHILD, PRESCHOOL; DEVELOPMENTAL DISABILITIES; EMBRYO, NONMAMMALIAN; FEMALE; HUMANS; INFANT; MALE; MICE; MICROCEPHALY; MUTATION, MISSENSE; PEDIGREE; PHENOTYPE; RAC1 GTP-BINDING PROTEIN; ZEBRAFISH;

EID: 85029537872     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2017.08.007     Document Type: Article

References (45)

1. Sheridan, E., Wright, J., Small, N., Corry, P.C., Oddie, S., Whibley, C., Petherick, E.S., Malik, T., Pawson, N., McKinney, P.A., Parslow, R.C., Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study. Lancet 382 (2013), 1350–1359.
2. Ropers, H.H., Genetics of early onset cognitive impairment. Annu. Rev. Genomics Hum. Genet. 11 (2010), 161–187.
3. Deciphering Developmental Disorders Study. Prevalence and architecture of de novo mutations in developmental disorders. Nature 542 (2017), 433–438.
4. Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E., et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515 (2014), 216–221.
5. Deciphering Developmental Disorders Study. Large-scale discovery of novel genetic causes of developmental disorders. Nature 519 (2015), 223–228.
6. Lelieveld, S.H., Reijnders, M.R., Pfundt, R., Yntema, H.G., Kamsteeg, E.J., de Vries, P., de Vries, B.B., Willemsen, M.H., Kleefstra, T., Löhner, K., et al. Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Nat. Neurosci. 19 (2016), 1194–1196.
7. MacArthur, D.G., Manolio, T.A., Dimmock, D.P., Rehm, H.L., Shendure, J., Abecasis, G.R., Adams, D.R., Altman, R.B., Antonarakis, S.E., Ashley, E.A., et al. Guidelines for investigating causality of sequence variants in human disease. Nature 508 (2014), 469–476.
8. Rauen, K.A., The RASopathies. Annu. Rev. Genomics Hum. Genet. 14 (2013), 355–369.
9. Van Aelst, L., D'Souza-Schorey, C., Rho GTPases and signaling networks. Genes Dev. 11 (1997), 2295–2322.
10. Heasman, S.J., Ridley, A.J., Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat. Rev. Mol. Cell Biol. 9 (2008), 690–701.
11. Duquette, P.M., Lamarche-Vane, N., Rho GTPases in embryonic development. Small GTPases, 5, 2014, 8.
12. Stankiewicz, T.R., Linseman, D.A., Rho family GTPases: key players in neuronal development, neuronal survival, and neurodegeneration. Front. Cell. Neurosci., 8, 2014, 314.
13. Aspenström, P., Fransson, A., Saras, J., Rho GTPases have diverse effects on the organization of the actin filament system. Biochem. J. 377 (2004), 327–337.
14. Boureux, A., Vignal, E., Faure, S., Fort, P., Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol. Biol. Evol. 24 (2007), 203–216.
15. Tahirovic, S., Hellal, F., Neukirchen, D., Hindges, R., Garvalov, B.K., Flynn, K.C., Stradal, T.E., Chrostek-Grashoff, A., Brakebusch, C., Bradke, F., Rac1 regulates neuronal polarization through the WAVE complex. J. Neurosci. 30 (2010), 6930–6943.
16. Wojnacki, J., Quassollo, G., Marzolo, M.P., Cáceres, A., Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics. Small GTPases, 5, 2014, e28430.
17. Saci, A., Cantley, L.C., Carpenter, C.L., Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size. Mol. Cell 42 (2011), 50–61.
18. Sugihara, K., Nakatsuji, N., Nakamura, K., Nakao, K., Hashimoto, R., Otani, H., Sakagami, H., Kondo, H., Nozawa, S., Aiba, A., Katsuki, M., Rac1 is required for the formation of three germ layers during gastrulation. Oncogene 17 (1998), 3427–3433.
19. Threadgill, R., Bobb, K., Ghosh, A., Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42. Neuron 19 (1997), 625–634.
20. Leone, D.P., Srinivasan, K., Brakebusch, C., McConnell, S.K., The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain. Dev. Neurobiol. 70 (2010), 659–678.
21. Chen, L., Melendez, J., Campbell, K., Kuan, C.Y., Zheng, Y., Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly. Dev. Biol. 325 (2009), 162–170.
22. Sobreira, N., Schiettecatte, F., Valle, D., Hamosh, A., GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum. Mutat. 36 (2015), 928–930.
23. Matos, P., Skaug, J., Marques, B., Beck, S., Veríssimo, F., Gespach, C., Boavida, M.G., Scherer, S.W., Jordan, P., Small GTPase Rac1: structure, localization, and expression of the human gene. Biochem. Biophys. Res. Commun. 277 (2000), 741–751.
24. Lek, M., Karczewski, K.J., Minikel, E.V., Samocha, K.E., Banks, E., Fennell, T., O'Donnell-Luria, A.H., Ware, J.S., Hill, A.J., Cummings, B.B., et al., Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536 (2016), 285–291.
25. Jordan, P., Brazåo, R., Boavida, M.G., Gespach, C., Chastre, E., Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene 18 (1999), 6835–6839.
26. Colicelli, J., Human RAS superfamily proteins and related GTPases. Sci. STKE, 2004, 2004, RE13.
27. Hobbs, G.A., Mitchell, L.E., Arrington, M.E., Gunawardena, H.P., DeCristo, M.J., Loeser, R.F., Chen, X., Cox, A.D., Campbell, S.L., Redox regulation of Rac1 by thiol oxidation. Free Radic. Biol. Med. 79 (2015), 237–250.
28. Gao, Y., Xing, J., Streuli, M., Leto, T.L., Zheng, Y., Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors. J. Biol. Chem. 276 (2001), 47530–47541.
29. De Baets, G., Van Durme, J., Reumers, J., Maurer-Stroh, S., Vanhee, P., Dopazo, J., Schymkowitz, J., Rousseau, F., SNPeffect 4.0: on-line prediction of molecular and structural effects of protein-coding variants. Nucleic Acids Res. 40 (2012), D935–D939.
30. Price, L.S., Leng, J., Schwartz, M.A., Bokoch, G.M., Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol. Biol. Cell 9 (1998), 1863–1871.
31. Ridley, A.J., Paterson, H.F., Johnston, C.L., Diekmann, D., Hall, A., The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 70 (1992), 401–410.
32. Machesky, L.M., Hall, A., Role of actin polymerization and adhesion to extracellular matrix in Rac- and Rho-induced cytoskeletal reorganization. J. Cell Biol. 138 (1997), 913–926.
33. Michiels, F., Habets, G.G., Stam, J.C., van der Kammen, R.A., Collard, J.G., A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 375 (1995), 338–340.
34. Jao, L.E., Wente, S.R., Chen, W., Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc. Natl. Acad. Sci. USA 110 (2013), 13904–13909.
35. Perles, Z., Moon, S., Ta-Shma, A., Yaacov, B., Francescatto, L., Edvardson, S., Rein, A.J., Elpeleg, O., Katsanis, N., A human laterality disorder caused by a homozygous deleterious mutation in MMP21. J. Med. Genet. 52 (2015), 840–847.
36. Mulherkar, S., Uddin, M.D., Couvillon, A.D., Sillitoe, R.V., Tolias, K.F., The small GTPases RhoA and Rac1 regulate cerebellar development by controlling cell morphogenesis, migration and foliation. Dev. Biol. 394 (2014), 39–53.
37. Nevado, J., Rosenfeld, J.A., Mena, R., Palomares-Bralo, M., Vallespín, E., Ángeles Mori, M., Tenorio, J.A., Gripp, K.W., Denenberg, E., Del Campo, M., et al. PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. Eur. J. Hum. Genet. 23 (2015), 1615–1626.
38. Van Dijck, A., van der Werf, I.M., Reyniers, E., Scheers, S., Azage, M., Siefkas, K., Van der Aa, N., Lacroix, A., Rosenfeld, J., Argiropoulos, B., et al. Five patients with a chromosome 1q21.1 triplication show macrocephaly, increased weight and facial similarities. Eur. J. Med. Genet. 58 (2015), 503–508.
39. Shinawi, M., Liu, P., Kang, S.H., Shen, J., Belmont, J.W., Scott, D.A., Probst, F.J., Craigen, W.J., Graham, B.H., Pursley, A., et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J. Med. Genet. 47 (2010), 332–341.
40. Rivière, J.B., Mirzaa, G.M., O'Roak, B.J., Beddaoui, M., Alcantara, D., Conway, R.L., St-Onge, J., Schwartzentruber, J.A., Gripp, K.W., Nikkel, S.M., et al., Finding of Rare Disease Genes (FORGE) Canada Consortium. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat. Genet. 44 (2012), 934–940.
41. Rosner, M., Hanneder, M., Siegel, N., Valli, A., Fuchs, C., Hengstschläger, M., The mTOR pathway and its role in human genetic diseases. Mutat. Res. 659 (2008), 284–292.
42. Hetmanski, J.H.R., Schwartz, J.M., Caswell, P.T., Rationalizing Rac1 and RhoA GTPase signaling: A mathematical approach. Small GTPases, 2016, 1–6.
43. Pengelly, R.J., Greville-Heygate, S., Schmidt, S., Seaby, E.G., Jabalameli, M.R., Mehta, S.G., Parker, M.J., Goudie, D., Fagotto-Kaufmann, C., Mercer, C., et al., DDD Study. Mutations specific to the Rac-GEF domain of TRIO cause intellectual disability and microcephaly. J. Med. Genet., 2016 jmedgenet-2016-103942.
44. Ba, W., Yan, Y., Reijnders, M.R., Schuurs-Hoeijmakers, J.H., Feenstra, I., Bongers, E.M., Bosch, D.G., De Leeuw, N., Pfundt, R., Gilissen, C., et al. TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function. Hum. Mol. Genet. 25 (2016), 892–902.
45. Hollstein, R., Parry, D.A., Nalbach, L., Logan, C.V., Strom, T.M., Hartill, V.L., Carr, I.M., Korenke, G.C., Uppal, S., Ahmed, M., et al. HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome. J. Med. Genet. 52 (2015), 797–803.