A Novel Homozygous RAB27A Mutation is Associated with Griscelli Syndrom type II and Less Severe Presentations
-
Mostafa Kamali
,
Sepideh Shahkarami
,
Elham Rayzan
,
Iraj Mohammazadeh
,
Meino Rohlfs
,
Christoph Klein
,
Nima Rezaei
Abstract
Background: Griscelli syndrome type II is a primary immunodeficiency disorder caused by RAB27A gene mutation and is inherited in an autosomal recessive manner and characterized by oculocutaneous hypopigmentation and various cellular immune system deficiencies.
Case Presentation: Herein, we report a 5-year-old girl with silvery-gray hair, eyebrows, and eyelashes who were referred to our primary immune deficiency clinic because of recurrent oral thrush. Further investigations were performed to uncover the probable underlying genetic disorder. Whole-exome sequencing revealed a novel mutation in the RAB27A gene (c.137T>G) and confirmed the diagnosis of Griscelli syndrome type 2.
Conclusions: Due to the poor prognosis nature of this disorder and also its need for differential diagnosis with some other conditions with hypopigmentation, prompt diagnosis, genetic analysis, and proper treatment are necessary for avoiding serious complications.
1. Al-Herz W, Bousfiha A, Casanova J-L, et al. Corrigendum: Primary immunodeficiency diseases: An update on the classification from the International Union of Immunological Societies Expert Committee for primary immunodeficiency. Front immunol 2014;5:460.
2. Tomita Y and Suzuki T. Genetics of pigmentary disorders. Am J Med Genet C Semin Med Genet 2004;131C:75-81.
3. Rezaei N, Moazzami K, Aghamohammadi A, et al. Neutropenia and primary immunodeficiency diseases. Int Rev Immunol 2009;28:335-366.
4. Klein C, Philippe N, Le Deist F, et al. Partial albinism with immunodeficiency (Griscelli syndrome). J Pediatr 1994;125:886-895.
5. Rezaei N, Aghamohammadi A, Notarangelo LD. Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. 1st ed. Velag Berlin Heidelberg: Springer, 2016.
6. Menasche G, Pastural E, Feldmann J, et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet 2000;25:173-176.
7. Wilson SM, Yip R, Swing DA, et al. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci U S A 2000;97:7933-7938.
8. Ménasché G, Fischer A, de Saint Basile G. Griscelli syndrome types 1 and 2. Am J Hum Genet
2002;71:1237-1238.
9. Kharkar V, Pande S, Mahajan S, et al. Griscelli syndrome: a new phenotype with circumscribed pigment loss? Dermatol Online J 2007;13:17.
10. Meeths M, Bryceson YT, Rudd E, et al. Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. Pediatr Blood Cancer 2010;54:563-572.
11. Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009;1:127-131.
12. Filipovich AH. Life‐threatening hemophagocytic syndromes: Current outcomes with hematopoietic stem cell transplantation. Pediatr Transplantat 2009;9:87-91.
13. Henter JI, Horne A, Aricó M, et al. HLH‐2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-131.
14. Hamidieh AA, Pourpak Z, Yari K, et al. Hematopoietic stem cell transplantation with a reduced‐intensity conditioning regimen in pediatric patients with G riscelli syndrome type 2. Pediatr Transplantat 2013;17:487-491.
15. Griscelli C, Durandy A, Guy-Grand D, et al. A syndrome associating partial albinism and immunodeficiency. Am J Med 1978;65:691-702.
16. Szczawinska-Poplonyk A, Kycler Z, Breborowicz A, et al. Pulmonary lymphomatoid granulomatosis in Griscelli syndrome type 2. Viral Immunol 2011;24:471-473.
17. Durmaz A, Ozkinay F, Onay H, et al. Molecular analysis and clinical findings of Griscelli syndrome patients. J Pediatr Hematol Oncol 2012;34:541-544.
18. Pastural E, Ersoy F, Yalman N, et al. Two genes are responsible for Griscelli syndrome at the same 15q21 locus. Genomics 2000;63:299-306.
19. Singh A, Garg A, Kapoor S, et al. An Indian boy with griscelli syndrome type 2: case report and review of literature. Indian J Dermatol 2014;59:394-397.
20. Figueiredo AC, Wasmeier C, Tarafder AK, et al. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem 2008;283:23209-23216.
21. Mamishi S, Modarressi MH, Pourakbari B, et al. Analysis of RAB27A gene in griscelli syndrome type 2: novel mutations including a deletion hotspot. J Clin Immunol 2008;28:384-389.
22. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-131.
23. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007;166:95-109.
24. Shamsian BS, Norbakhsh K, Rezaei N, et al. A novel RAB27A mutation in a patient with Griscelli syndrome type 2. J Investig Allergol Clin Immunol 2010;20:612-615.
25. Rezaei N, Pourpak Z, Aghamohammadi A, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry. Am J Reprod Immunol 2006;56:145-151.
2. Tomita Y and Suzuki T. Genetics of pigmentary disorders. Am J Med Genet C Semin Med Genet 2004;131C:75-81.
3. Rezaei N, Moazzami K, Aghamohammadi A, et al. Neutropenia and primary immunodeficiency diseases. Int Rev Immunol 2009;28:335-366.
4. Klein C, Philippe N, Le Deist F, et al. Partial albinism with immunodeficiency (Griscelli syndrome). J Pediatr 1994;125:886-895.
5. Rezaei N, Aghamohammadi A, Notarangelo LD. Primary Immunodeficiency Diseases: Definition, Diagnosis, and Management. 1st ed. Velag Berlin Heidelberg: Springer, 2016.
6. Menasche G, Pastural E, Feldmann J, et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet 2000;25:173-176.
7. Wilson SM, Yip R, Swing DA, et al. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci U S A 2000;97:7933-7938.
8. Ménasché G, Fischer A, de Saint Basile G. Griscelli syndrome types 1 and 2. Am J Hum Genet
2002;71:1237-1238.
9. Kharkar V, Pande S, Mahajan S, et al. Griscelli syndrome: a new phenotype with circumscribed pigment loss? Dermatol Online J 2007;13:17.
10. Meeths M, Bryceson YT, Rudd E, et al. Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. Pediatr Blood Cancer 2010;54:563-572.
11. Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009;1:127-131.
12. Filipovich AH. Life‐threatening hemophagocytic syndromes: Current outcomes with hematopoietic stem cell transplantation. Pediatr Transplantat 2009;9:87-91.
13. Henter JI, Horne A, Aricó M, et al. HLH‐2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-131.
14. Hamidieh AA, Pourpak Z, Yari K, et al. Hematopoietic stem cell transplantation with a reduced‐intensity conditioning regimen in pediatric patients with G riscelli syndrome type 2. Pediatr Transplantat 2013;17:487-491.
15. Griscelli C, Durandy A, Guy-Grand D, et al. A syndrome associating partial albinism and immunodeficiency. Am J Med 1978;65:691-702.
16. Szczawinska-Poplonyk A, Kycler Z, Breborowicz A, et al. Pulmonary lymphomatoid granulomatosis in Griscelli syndrome type 2. Viral Immunol 2011;24:471-473.
17. Durmaz A, Ozkinay F, Onay H, et al. Molecular analysis and clinical findings of Griscelli syndrome patients. J Pediatr Hematol Oncol 2012;34:541-544.
18. Pastural E, Ersoy F, Yalman N, et al. Two genes are responsible for Griscelli syndrome at the same 15q21 locus. Genomics 2000;63:299-306.
19. Singh A, Garg A, Kapoor S, et al. An Indian boy with griscelli syndrome type 2: case report and review of literature. Indian J Dermatol 2014;59:394-397.
20. Figueiredo AC, Wasmeier C, Tarafder AK, et al. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem 2008;283:23209-23216.
21. Mamishi S, Modarressi MH, Pourakbari B, et al. Analysis of RAB27A gene in griscelli syndrome type 2: novel mutations including a deletion hotspot. J Clin Immunol 2008;28:384-389.
22. Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-131.
23. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 2007;166:95-109.
24. Shamsian BS, Norbakhsh K, Rezaei N, et al. A novel RAB27A mutation in a patient with Griscelli syndrome type 2. J Investig Allergol Clin Immunol 2010;20:612-615.
25. Rezaei N, Pourpak Z, Aghamohammadi A, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry. Am J Reprod Immunol 2006;56:145-151.
| Files | ||
| Issue | Vol 7, No 2 (2024) | |
| Section | Case Report | |
| DOI | https://doi.org/10.18502/igj.v7i2.17854 | |
| Keywords | ||
| Griscelli Syndrome Type II Novel Mutation Primary Immunodeficiency Disorder RAB27A Gene | ||
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How to Cite
1.
Kamali M, Shahkarami S, Rayzan E, Mohammazadeh I, Rohlfs M, Klein C, Rezaei N. A Novel Homozygous RAB27A Mutation is Associated with Griscelli Syndrom type II and Less Severe Presentations. Immunol Genet J. 2024;7(2):82-86.
