A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families
<p>Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the <em>RAB27A</em> gene and characterized by partial albinism, immunodeficiency, and occasional hematological and neurological involvement. We reviewed and analyzed the medic...
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , |
| منشور في: |
2020
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513555852689408 |
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| author | Reem Al‐Sulaiman (14776948) |
| author2 | Amna Othman (14152659) Karen El‐Akouri (14776951) Shehab Fareed (14776954) Hajer AlMulla (14776957) Aseel Sukik (14571102) Mariam Al‐Mureikhi (14776960) Noora Shahbeck (14152671) Rehab Ali (14152668) Fatma Al‐Mesaifri (14776963) Sara Musa (14152662) Mariam Al‐Mulla (14776966) Khalid Ibrahim (3853360) Khalid Mohamed (7572353) Maryam Ali Al‐Nesef (14776969) Mohammad Ehlayel (14776972) Tawfeg Ben‐Omran (14776975) |
| author2_role | author author author author author author author author author author author author author author author author |
| author_facet | Reem Al‐Sulaiman (14776948) Amna Othman (14152659) Karen El‐Akouri (14776951) Shehab Fareed (14776954) Hajer AlMulla (14776957) Aseel Sukik (14571102) Mariam Al‐Mureikhi (14776960) Noora Shahbeck (14152671) Rehab Ali (14152668) Fatma Al‐Mesaifri (14776963) Sara Musa (14152662) Mariam Al‐Mulla (14776966) Khalid Ibrahim (3853360) Khalid Mohamed (7572353) Maryam Ali Al‐Nesef (14776969) Mohammad Ehlayel (14776972) Tawfeg Ben‐Omran (14776975) |
| author_role | author |
| dc.creator.none.fl_str_mv | Reem Al‐Sulaiman (14776948) Amna Othman (14152659) Karen El‐Akouri (14776951) Shehab Fareed (14776954) Hajer AlMulla (14776957) Aseel Sukik (14571102) Mariam Al‐Mureikhi (14776960) Noora Shahbeck (14152671) Rehab Ali (14152668) Fatma Al‐Mesaifri (14776963) Sara Musa (14152662) Mariam Al‐Mulla (14776966) Khalid Ibrahim (3853360) Khalid Mohamed (7572353) Maryam Ali Al‐Nesef (14776969) Mohammad Ehlayel (14776972) Tawfeg Ben‐Omran (14776975) |
| dc.date.none.fl_str_mv | 2020-08-28T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1002/ajmg.a.61829 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_founder_RAB27A_variant_causes_Griscelli_syndrome_type_2_with_phenotypic_heterogeneity_in_Qatari_families/22257484 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences founder effect GS2 HLH Qatari RAB27A |
| dc.title.none.fl_str_mv | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the <em>RAB27A</em> 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 <em>RAB27A</em> 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. </p> <h2>Other Information</h2> <p>Published in: American Journal of Medical Genetics Part A<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1002/ajmg.a.61829" target="_blank">http://dx.doi.org/10.1002/ajmg.a.61829</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_be721e3af79555ded49100e4f9aa07ea |
| identifier_str_mv | 10.1002/ajmg.a.61829 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22257484 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari familiesReem Al‐Sulaiman (14776948)Amna Othman (14152659)Karen El‐Akouri (14776951)Shehab Fareed (14776954)Hajer AlMulla (14776957)Aseel Sukik (14571102)Mariam Al‐Mureikhi (14776960)Noora Shahbeck (14152671)Rehab Ali (14152668)Fatma Al‐Mesaifri (14776963)Sara Musa (14152662)Mariam Al‐Mulla (14776966)Khalid Ibrahim (3853360)Khalid Mohamed (7572353)Maryam Ali Al‐Nesef (14776969)Mohammad Ehlayel (14776972)Tawfeg Ben‐Omran (14776975)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesfounder effectGS2HLHQatariRAB27A<p>Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disorder caused by pathogenic variants in the <em>RAB27A</em> 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 <em>RAB27A</em> 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. </p> <h2>Other Information</h2> <p>Published in: American Journal of Medical Genetics Part A<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br> See article on publisher's website: <a href="http://dx.doi.org/10.1002/ajmg.a.61829" target="_blank">http://dx.doi.org/10.1002/ajmg.a.61829</a></p>2020-08-28T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/ajmg.a.61829https://figshare.com/articles/journal_contribution/A_founder_RAB27A_variant_causes_Griscelli_syndrome_type_2_with_phenotypic_heterogeneity_in_Qatari_families/22257484CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/222574842020-08-28T06:00:00Z |
| spellingShingle | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families Reem Al‐Sulaiman (14776948) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences founder effect GS2 HLH Qatari RAB27A |
| status_str | publishedVersion |
| title | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| title_full | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| title_fullStr | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| title_full_unstemmed | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| title_short | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| title_sort | A founder RAB27A variant causes Griscelli syndrome type 2 with phenotypic heterogeneity in Qatari families |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences founder effect GS2 HLH Qatari RAB27A |