Rai1 gene mutations: Mechanisms of Smith–Magenis syndrome

Application of Clinical Genetics

Volumn 10, Issue , 2017, Pages 85-94

  Falco, Mariateresa ^a   Amabile, Sonia ^a   Acquaviva, Fabio ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

17p11.2; Craniofacial abnormalities; Neurogenesis; Sleep disorders; Syndromic obesity

Indexed keywords

TRANSCRIPTION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; BEHAVIOR; BONE DEVELOPMENT; CELL CYCLE REGULATION; CELL GROWTH; CHROMOSOME 17P; CHROMOSOME DELETION; CIRCADIAN RHYTHM; CLINICAL FEATURE; COGNITIVE DEFECT; CRANIOFACIAL MALFORMATION; EMBRYO; GENE; GENE DELETION; GENE EXPRESSION; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC DIFFERENCE; GENETIC VARIATION; GLUCOSE METABOLISM; HUMAN; LIPID METABOLISM; MENTAL DISEASE; MOUSE; MUSCLE HYPOTONIA; MUTATIONAL ANALYSIS; NERVE CELL DIFFERENTIATION; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; OBESITY; OVERNUTRITION; PHENOTYPE; RAI1 GENE; REVIEW; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY; SLEEP DISORDER; SMITH MAGENIS SYNDROME;

EID: 85041817422     PISSN: None     EISSN: 1178704X     Source Type: Journal    
DOI: 10.2147/TACG.S128455     Document Type: Review

References (95)

1. Smith ACM. Deletion of the 17 short arm in 2 patients with facial clefts and congenital heart-disease. Am J Hum Genet. 1982;32(6):A146.
2. Smith AC, Magenis RE, Elsea SH. Overview of Smith-Magenis syndrome. J Assoc Genet Technol. 2005;31(4):163–167.
3. Greenberg F, Guzzetta V, MontesdeOca-Luna R, et al. Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2). Am J Hum Genet. 1991;49(6):1207–1218.
4. Elsea SH, Girirajan S. Smith–Magenis syndrome. Eur J Hum Genet. 2008;16(4):412–421.
5. Smith AC, McGavran L, Robinson J, et al. Interstitial deletion of (17) (p11.2p11.2) in nine patients. Am J Med Genet. 1986;24(3):393–414.
6. Slager RE, Newton TL, Vlangos CN, Finucane B, Elsea SH. Mutations in RAI1 associated with Smith–Magenis syndrome. Nat Genet. 2003;33(4):466–468.
7. Zori RT, Lupski JR, Heju Z, et al. Clinical, cytogenetic, and molecular evidence for an infant with Smith-Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion. Am J Med Genet. 1993;47(4):504–511.
8. Campbell IM, Yuan B, Robberecht C, et al. Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders. Am J Hum Genet. 2014;95(2):173–182.
9. Acquaviva F, Sana ME, Della Monica M, et al. First evidence of Smith-Magenis syndrome in mother and daughter due to a novel RAI mutation. Am J Med Genet A. 2017;173(1):231–238.
10. Juyal RC, Figuera LE, Hauge X, et al. Molecular analyses of 17p11.2 deletions in 62 Smith-Magenis syndrome patients. Am J Hum Genet. 1996;58(5):998–1007.
11. Chen KS, Manian P, Koeuth T, et al. Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndrome. Nat Genet. 1997;17(2):154–163.
12. Bi W, Saifi GM, Shaw CJ, et al. Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. Hum Genet. 2004;115(6):515–524.
13. Girirajan S, Elsas LJ, Devriendt K, Elsea SH. RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. J Med Genet. 2005;42(11):820–828.
14. Edelman EA, Girirajan S, Finucane B, et al. Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases. Clin Genet. 2007;71(6):540–550.
15. Girirajan S, Vlangos CN, Szomju BB, et al. Genotype-phenotype correlation in Smith-Magenis syndrome: evidence that multiple genes in 17p11.2 contribute to the clinical spectrum. Genet Med. 2006;8(7):417–427.
16. Ricard G, Molina J, Chrast J, et al. Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models. PLoS Biol. 2010;8(11):e1000543.
17. Yan J, Bi W, Lupski JR. Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. Am J Hum Genet. 2007;80(3):518–525.
18. Greenberg F, Lewis RA, Potocki L, et al. Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2). Am J Med Genet. 1996;62(3):247–254.
19. Dykens EMM, Smith ACC. Distinctiveness and correlates of mal-adaptive behaviour in children and adolescents with Smith-Magenis syndrome. J Intellect Disabil Res. 1998;42(Pt 6):481–489.
20. Smith AC, Dykens E, Greenberg F. Behavioral phenotype of Smith-Magenis syndrome (del 17p11.2). Am J Med Genet. 1998;81(2):179–185.
21. Smith AC, Gropman AL, Bailey-Wilson JE, et al. Hypercholesterolemia in children with Smith-Magenis syndrome: del (17) (p11.2p11.2). Genet Med. 2002;4(3):118–125.
22. Dubourg C, Bonnet-Brilhault F, Toutain A, et al. Identification of nine new RAI1-truncating mutations in Smith-Magenis syndrome patients without 17p11.2 deletions. Mol Syndromol. 2014;5(2):57–64.
23. Finucane BM, Konar D, Haas-Givler B, Kurtz MB, Scott CI Jr. The spasmodic upper-body squeeze: a characteristic behavior in Smith-Magenis syndrome. Dev Med Child Neurol. 1994;36(1):78–83.
24. Truong HT, Dudding T, Blanchard CL, Elsea SH. Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature. BMC Med Genet. 2010;11(1):142.
25. Smith ACM, Gropman A. Smith-Magenis syndrome. 3rd ed. In: Cassidy SB, Allanson JE, editors. Management of Genetic Syndromes. Hoboken, NJ: John Wiley & Sons, Inc.; 2010:739–768.
26. Allanson JE, Greenberg F, Smith AC. The face of Smith-Magenis syndrome: a subjective and objective study. J Med Genet. 1999;36(5): 394–397.
27. Tomona N, Smith AC, Guadagnini JP, Hart TC. Craniofacial and dental phenotype of Smith–Magenis syndrome. Am J Med Genet A. 2006;140A(23):2556–2561.
28. Sarimski K. Communicative competence and behavioural phenotype in children with Smith-Magenis syndrome. Genet Couns. 2004;15(3):347–355.
29. Gropman AL, Duncan WC, Smith AC. Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2). Pediatr Neurol. 2006;34(5):337–350.
30. Wolters PL, Gropman AL, Martin SC, et al. Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome. Pediatr Neurol. 2009;41(4):250–258.
31. Hildenbrand HL, Smith AC. Analysis of the sensory profile in children with Smith-Magenis syndrome. Phys Occup Ther Pediatr. 2012;32(1):48–65.
32. Laje G, Morse R, Richter W, Ball J, Pao M, Smith AC. Autism spectrum features in Smith-Magenis syndrome. Am J Med Genet C Semin Med Genet. 2010;154(4):456–462.
33. Arron K, Oliver C, Moss J, Berg K, Burbidge C. The prevalence and phenomenology of self-injurious and aggressive behaviour in genetic syndromes. J Intellect Disabil Res. 2011;55(2):109–120.
34. Sloneem J, Oliver C, Udwin O, Woodcock KA. Prevalence, phenomenology, aetiology and predictors of challenging behaviour in Smith-Magenis syndrome. J Intellect Disabil Res. 2011;55(2):138–151.
35. Finucane B, Dirrigl KH, Simon EW. Characterization of self-injurious behaviors in children and adults with Smith-Magenis syndrome. Am J Ment Retard. 2001;106(1):52–58.
36. Alaimo JT, Barton LV, Mullegama SV, Wills RD, Foster RH, Elsea SH. Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome. Res Dev Disabil. 2015;47:27–38.
37. Burns B, Schmidt K, Williams SR, Kim S, Girirajan S, Elsea SH. Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome. Hum Mol Genet. 2010;19(20):4026–4042.
38. Foster RH, Kozachek S, Stern M, Elsea SH. Caring for the caregivers: an investigation of factors related to well-being among parents caring for a child with Smith-Magenis syndrome. J Genet Couns. 2010;19(2):187–198.
39. Potocki L, Glaze D, Tan DX, et al. Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome. J Med Genet. 2000;37(6):428–433.
40. De Leersnyder H, De Blois MC, Claustrat B, et al. Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome. J Pediatr. 2001;139(1):111–116.
41. Boone PM, Reiter RJ, Glaze DG, Tan DX, Lupski JR, Potocki L. Abnormal circadian rhythm of melatonin in Smith-Magenis syndrome patients with RAI1 point mutations. Am J Med Genet A. 2011;155(8): 2024–2027.
42. Boudreau EA, Johnson KP, Jackman AR, et al. Review of disrupted sleep patterns in Smith-Magenis syndrome and normal melatonin secretion in a patient with an atypical interstitial 17p11.2 deletion. Am J Med Genet A. 2009;149(7):1382–1391.
43. Schoumans J, Staaf J, Jönsson G, et al. Detection and delineation of an unusual 17p11.2 deletion by array-CGH and refinement of the Smith-Magenis syndrome minimum deletion to approximately 650 kb. Eur J Med Genet. 2005;48(3):290–300.
44. Vlangos CN, Yim DK, Elsea SH. Refinement of the Smith-Magenis syndrome critical region to approximately 950kb and assessment of 17p11.2 deletions. Are all deletions created equally? Mol Genet Metab. 2003;79(2):134–141.
45. Vlangos CN, Wilson M, Blancato J, Smith AC, Elsea SH. Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene. Am J Med Genet A. 2005;132A(3):278–282.
46. Liburd N, Ghosh M, Riazuddin S, et al. Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome. Hum Genet. 2001;109(5):535–541.
47. Wang A, Liang Y, Fridell RA, et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science. 1998;280(5368):1447–1451.
48. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–834.
49. Nickerson ML, Warren MB, Toro JR, et al. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2002;2(2):157–164.
50. Dardour L, Verleyen P, Lesage K, Holvoet M, Devriendt K. Bilateral renal tumors in an adult man with Smith-Magenis syndrome: the role of the FLCN gene. Eur J Med Genet. 2016;59(10):499–501.
51. Carney G, Wei S, Rizzo WB. Sjögren-Larsson syndrome: seven novel mutations in the fatty aldehyde dehydrogenase gene ALDH3A2. Hum Mutat. 2004;24(2):186.
52. Imai Y, Suzuki Y, Matsui T, Tohyama M, Wanaka A, Takagi T. Cloning of a retinoic acid-induced gene, GT1, in the embryonal carcinoma cell line P19: neuron-specific expression in the mouse brain. Brain Res Mol Brain Res. 1995;31(1–2):1–9.
53. Walz K, Caratini-Rivera S, Bi W, et al. Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance. Mol Cell Biol. 2003;23(10):3646–3655.
54. Bi W, Yan J, Shi X, et al. Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes. Hum Mol Genet. 2007;16(15):1802–1813.
55. Toulouse A, Rochefort D, Roussel J, Joober R, Rouleau GA. Molecular cloning and characterization of human RAI1, a gene associated with schizophrenia. Genomics. 2003;82(2):162–171.
56. Fragoso YD, Stoney PN, Shearer KD, et al. Expression in the human brain of retinoic acid induced 1, a protein associated with neurobehavioural disorders. Brain Struct Funct. 2015;220(2):1195–1203.
57. Seranski P, Hoff C, Radelof U, et al. RAI1 is a novel polyglutamine encoding gene that is deleted in Smith-Magenis syndrome patients. Gene. 2001;270(1–2):69–76.
58. Vulto-van Silfhout AT, Rajamanickam S, Jensik PJ, et al. Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems. Am J Hum Genet. 2014;94(5):649–661.
59. Faqeih EA, Al-Owain M, Colak D, et al. Novel homozygous DEAF1 variant suspected in causing white matter disease, intellectual disability, and microcephaly. Am J Med Genet A. 2014;164A(6): 1565–1570.
60. Luo T, Wagner E, Crandall JE, Dräger UC. A retinoic-acid critical period in the early postnatal mouse brain. Biol Psychiatry. 2004;56(12):971–980.
61. Chen L, Tao Y, Song F, Yuan X, Wang J, Saffen D. Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain. Sci Rep. 2016;6:19010.
62. Berger SI, Ciccone C, Simon KL, et al. Exome analysis of Smith-Magenis-like syndrome cohort identifies de novo likely pathogenic variants. Hum Genet. 2017;136(4):409–420.
63. Carmona-Mora P, Encina CA, Canales CP, et al. Functional and cellular characterization of human Retinoic Acid Induced 1 (RAI1) mutations associated with Smith-Magenis Syndrome. BMC Mol Biol. 2010;11(1):63.
64. Huang WH, Guenthner CJ, Xu J, et al. Molecular and neural functions of RAI1, the causal gene for Smith-Magenis syndrome. Neuron. 2016;92(2):392–406.
65. Girirajan S, Truong HT, Blanchard CL, Elsea SH. A functional network module for Smith-Magenis syndrome. Clin Genet. 2009;75(4):364–374.
66. Williams SR, Zies D, Mullegama SV, Grotewiel MS, Elsea SH. Smith-magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity. Am J Hum Genet. 2012;90(6):941–949.
67. Darvekar S, Johnsen SS, Eriksen AB, Johansen T, Sjøttem E. Identification of two independent nucleosome-binding domains in the transcriptional co-activator SPBP. Biochem J. 2012;442(1):65–75.
68. Yun M, Wu J, Workman JL, Li B. Readers of histone modifications. Cell Res. 2011;21(4):564–578.
69. Atanesyan L, Günther V, Dichtl B, Georgiev O, Schaffner W. Polyglutamine tracts as modulators of transcriptional activation from yeast to mammals. Biol Chem. 2012;393(1–2):63–70.
70. Vilboux T, Ciccone C, Blancato JK, et al. Molecular analysis of the Retinoic Acid Induced 1 gene (RAI1) in patients with suspected smith-magenis syndrome without the 17p11.2 deletion. PLoS One. 2011;6(8).
71. Bi W, Ohyama T, Nakamura H, et al. Inactivation of Rai1 in mice recapitulates phenotypes observed in chromosome engineered mouse models for Smith-Magenis syndrome. Hum Mol Genet. 2005;14(8):983–995.
72. Alaimo JT, Hahn NC, Mullegama SV, Elsea SH. Dietary regimens modify early onset of obesity in mice haploinsufficient for Rai1. PLoS One. 2014;9(8):e105077.
73. Tahir R, Kennedy A, Elsea SH, Dickinson AJ. Retinoic acid induced-1 (Rai1) regulates craniofacial and brain development in Xenopus. Mech Dev. 2014;133:91–104.
74. Chen L, Mullegama SV, Alaimo JT, Elsea SH. Smith-Magenis syndrome and its circadian influence on development, behavior, and obesity – own experience. Dev Period Med. 2015;19(2):149–156.
75. Carneiro BT, Araujo JF. The food-entrainable oscillator: a network of interconnected brain structures entrained by humoral signals? Chronobiol Int. 2009;26(7):1273–1289.
76. Noble EE, Billington CJ, Kotz CM, Wang C. The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1053–R1069.
77. Gray J, Yeo GS, Cox JJ, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2006;55(12):3366–3371.
78. Joober R, Benkelfat C, Toulouse A, et al. Analysis of 14 CAG repeat-containing genes in schizophrenia. Am J Med Genet. 1999;88(6):694–699.
79. Hayes S, Turecki G, Brisebois K, et al. CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2). Hum Mol Genet. 2000;9(12):1753–1758.
80. Potocki L, Bi W, Treadwell-Deering D, et al. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet. 2007;80(4):633–649.
81. van der Zwaag B, Franke L, Poot M, et al. Gene-network analysis identifies susceptibility genes related to glycobiology in autism. PLoS One. 2009;4(5):e5324.
82. Carmona-Mora P, Walz K. Retinoic acid induced 1, RAI1: a dosage sensitive gene related to neurobehavioral alterations including autistic behavior. Curr Genomics. 2010;11(8):607–617.
83. Redin C, Gérard B, Lauer J, et al. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J Med Genet. 2014;51(11):724–736.
84. Thaker VV, Esteves KM, Towne MC, et al. Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome. J Clin Endocrinol Metab. 2015;100(5): 1723–1730.
85. Churbanov AY, Karafet TM, Morozov L IV, et al. Whole exome sequencing reveals homozygous mutations in RAI1, OTOF, and SLC26A4 genes associated with nonsyndromic hearing loss in Altaian families (South Siberia). PLoS One. 2016;11(4):e0153841.
86. Barnett C, Yazgan O, Kuo HC, et al. Williams syndrome transcription factor is critical for neural crest cell function in Xenopus laevis. Mech Dev. 2012;129(9–12):324–338.
87. Hittner HM, King RA, Riccardi VM, et al. Oculocutaneous albinoidism as a manifestation of reduced neural crest derivatives in the Prader-Willi syndrome. Am J Ophthalmol. 1982;94(3):328–337.
88. Kochilas L, Merscher-Gomez S, Lu MM, et al. The role of neural crest during cardiac development in a mouse model of DiGeorge syndrome. Dev Biol. 2002;251(1):157–166.
89. Lim JH, Luo T, Sargent TD, Fallon JR. Developmental expression of Xenopus fragile X mental retardation-1 gene. Int J Dev Biol. 2005;49(8):981–984.
90. Roper RJ, VanHorn JF, Cain CC, Reeves RH. A neural crest deficit in Down syndrome mice is associated with deficient mitotic response to Sonic hedgehog. Mech Dev. 2009;126(3–4):212–219.
91. Wurdak H, Ittner LM, Lang KS, et al. Inactivation of TGFbeta signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome. Genes Dev. 2005;19(5):530–535.
92. Laje G, Bernert R, Morse R, Pao M, Smith AC. Pharmacological treatment of disruptive behavior in Smith-Magenis syndrome. Am J Med Genet C Semin Med Genet. 2010;154C(4):463–468.
93. Poisson A, Nicolas A, Cochat P, et al. Behavioral disturbance and treatment strategies in Smith-Magenis syndrome. Orphanet J Rare Dis. 2015;10(1):111.
94. De Leersnyder H, Bresson JL, de Blois MC, et al. Beta 1-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome. J Med Genet. 2003;40(1):74–78.
95. Loviglio MN, Beck CR, White JJ, et al. Identification of a RAI1-associated disease network through integration of exome sequencing, transcriptomics, and 3D genomics. Genome Med. 2016;8(1):105.