Hematopoietic stem cell transplantation in children with Griscelli syndrome type 2: a single-center report on 35 patients

Almofareh, Maha T; Ayas, Mouhab; Al-Seraihy, Amal; Siddiqui, Khawar; Al‐Jefri, Abdullah; Ghemlas, Ibrahim; Alsaedi, Hawazen Saleh; El-Solh, H; Al‐Sweedan, Suleimman; Al‐Saud, Bandar; Al‐Mousa, Hamoud; Al-Dhekri, Hasan; Arnaout, Rand; Mohammed, Reem; Al‐Muhsen, Saleh; Al-Ahmari, Ali

doi:10.1038/s41409-020-0885-6

Cited by 15 publications

(14 citation statements)

References 38 publications

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“…Types of reported pathogenic variants include missense, nonsense, and frameshift pathogenic variants (Aksu et al, 2003; Ashrafi et al, 2006; Harfi et al, 1992; Mamishi et al, 2008; Masri et al, 2008; Mishra et al, 2014; Ohbayashi et al, 2010; Patiroglu et al, 2016; Shamsian et al, 2010). Three of the 35 patients reported by Al‐Mofareh et al (2020) had the same RAB27A pathogenic variant p.R82C as our patients. Jin et al (2018) also reported the same RAB27A variant.…”

Section: Discussionsupporting

confidence: 75%

A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families

Alsulaiman

Othman

El‐Akouri

et al. 2020

American J of Med Genetics Pt A

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Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the RAB27A gene and characterized by partial albinism, immunodeficiency, and occasional hematological and neurological involvement. We reviewed and analyzed the medical records of 12 individuals with GS2 from six families belonging to a highly consanguineous Qatari tribe and with a recurrent pathogenic variant in the RAB27A gene (NM_004580.4: c.244C > T, p.Arg82Cys). Detailed demographic, clinical, and molecular data were collected. Cutaneous manifestations were the most common presentation (42%), followed by neurological abnormalities (33%) and immunodeficiency (25%). The most severe manifestation was HLH (33%). Among the 12 patients, three patients (25%) underwent HSCT, and four (33%) died. The cause of death in all four patients was deemed HLH, providing evidence for this complication's fatal nature. Interestingly, two affected patients (16%) were asymptomatic. This report highlights the broad spectrum of clinical presentations of GS2 associated with a founder variant in the RAB27A gene (c.244C > T, p.Arg82Cys). Early suspicion of GS2 among Qatari patients with cutaneous manifestations, neurological findings, immunodeficiency, and HLH would shorten the diagnostic odyssey, guide early and appropriate treatment, and prevent fatal outcomes.

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Section: Discussionsupporting

confidence: 75%

A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families

Alsulaiman

Othman

El‐Akouri

et al. 2020

American J of Med Genetics Pt A

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“…Previous studies have demonstrated that overall survival rate of HLA-matched HSCT in both diseases is approximately 70%; however, poor T-cell engraftment and immune function could develop unless conditioning prior to cell infusion was given. [31][32][33] We also identified a hemizygous variant in IL2RG, confirming the diagnosis of X-linked severe combined immunodeficiency (SCID) in patient 3 (Table 2). He was the second child with a healthy brother.…”

Section: Discussionsupporting

confidence: 66%

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort

Tengsujaritkul

Suratannon

Ittiwut

et al. 2021

Pediatric Allergy Immunology

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Background Inborn errors of immunity (IEI) comprise more than 400 rare diseases with potential life‐threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunologic, and genetic features of Thai pediatric patients with IEI. The use of whole‐exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods Thirty six unrelated patients with clinical and laboratory findings consistent with IEI were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results The median age of disease onset was 4 months (range: 1 month to 13 years), and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in IEI genes were identified. The clinical usefulness of WES in IEI was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

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“…Previous studies have demonstrated that overall survival rate of HLA-matched HSCT in both diseases are approximately 70%; however, poor T-cell engraftment and immune function could develop unless conditioning prior to cell infusion was given. [17][18][19] We also identified a hemizygous variant in IL2RG , confirming the diagnosis of X-linked severe combined immunodeficiency (SCID) in patient 3 (Table 2). He was the second child with a healthy brother.…”

Section: Discussionsupporting

confidence: 66%

Phenotypic Heterogeneity and Genotypic Spectrum of Primary Immunodeficiencies with Whole Exome Sequencing in a Thai Patient Cohort

Tengsujaritkul

Suratannon

Ittiwut

et al. 2021

Preprint

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Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

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Hematopoietic stem cell transplantation in children with Griscelli syndrome type 2: a single-center report on 35 patients

Cited by 15 publications

References 38 publications

A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families

A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families

Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort

Phenotypic Heterogeneity and Genotypic Spectrum of Primary Immunodeficiencies with Whole Exome Sequencing in a Thai Patient Cohort

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