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...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , |
| منشور في: |
2020
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إضافة وسم
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| الملخص: | <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> |
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