دورية أكاديمية
أعرض في EDS

A novel homozygous RTEL1 variant in a consanguineous Lebanese family: phenotypic heterogeneity and disease anticipation.

التفاصيل البيبلوغرافية
العنوان: A novel homozygous RTEL1 variant in a consanguineous Lebanese family: phenotypic heterogeneity and disease anticipation.
المؤلفون: Gutierrez-Rodrigues F; Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, 20892-1202, USA., Masri N; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon., Chouery E; Unité de Génétique Médicale, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon., Diamond C; Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, 20892-1202, USA., Jalkh N; Unité de Génétique Médicale, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon., Vicente A; Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, 20892-1202, USA., Kajigaya S; Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, 20892-1202, USA., Abillama F; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon., Bejjani N; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon., Serhal W; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon., Calado RT; Department of Medical Imaging, Hematology, and Clinical Oncology, University of São Paulo, Ribeirão Preto, SP, Brazil., Young NS; Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, 20892-1202, USA., Farhat H; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon. hussein.farhat@laumcrh.com., Coussa ML; LAU Gilbert and Rose-Marie Chagoury School of Medicine, LAUMC/RH, Zahar Street, Achrafieh, Beirut, 1110, Lebanon.
المصدر: Human genetics [Hum Genet] 2019 Dec; Vol. 138 (11-12), pp. 1323-1330. Date of Electronic Publication: 2019 Nov 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7613873 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1203 (Electronic) Linking ISSN: 03406717 NLM ISO Abbreviation: Hum Genet Subsets: MEDLINE
أسماء مطبوعة: Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer-Verlag.
مواضيع طبية MeSH: Consanguinity* , Homozygote* , Mutation*, DNA Helicases/*genetics , Genetic Diseases, Inborn/*epidemiology , Telomere/*genetics, Adolescent ; Adult ; Female ; Genetic Diseases, Inborn/genetics ; Humans ; Lebanon/epidemiology ; Male ; Middle Aged ; Pedigree ; Phenotype ; Young Adult
مستخلص: Phenotypic heterogeneity is often observed in patients with telomeropathies caused by pathogenic variants in telomere biology genes. However, the roles of recessive variants in these different phenotypes are not fully characterized. Our goal is to describe the biological roles of a novel homozygous RTEL1 variant identified in a consanguineous Lebanese family with unusual presentation of telomeropathies. A proband was screened for germline variants in telomere biology genes by whole exome sequencing. Leukocytes' telomere length was measured in the proband and eight relatives. We identified a novel homozygous p.E665K RTEL1 variant in the proband, his mother, and seven siblings that associated with telomere shortening and a broad spectrum of clinical manifestations, ranging from mild unspecific findings to severe phenotypes. Consanguinity in at least three family generations led to increased frequency of the homozygous p.E665K variant in the youngest generation and progressive telomere shortening. The increased frequency of the homozygous RTEL1 variant due to consanguinity in this Lebanese family allowed us to infer novel behaviors of recessive RTEL1 variants, as the expressivity and penetrance of this gene are very heterogenous between inter- and intra-generations. Progressive telomere shortening was associated with disease anticipation, first reported in recessive autosomal telomeropathies. Both genetic testing and telomere length measurement were critical for the clinical diagnosis of this family with telomere diseases marked by phenotypic heterogeneity.
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معلومات مُعتمدة: Z99 HL999999 United States ImNIH Intramural NIH HHS; 13/08135-2 São Paulo Research Foundation/CAPES
المشرفين على المادة: EC 3.6.1.- (RTEL1 protein, human)
EC 3.6.4.- (DNA Helicases)
تواريخ الأحداث: Date Created: 20191103 Date Completed: 20191206 Latest Revision: 20230105
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC9809984
DOI: 10.1007/s00439-019-02076-8
PMID: 31677132
قاعدة البيانات: MEDLINE
الوصف
تدمد:1432-1203
DOI:10.1007/s00439-019-02076-8