title: Carrier screening of RTEL1 mutations in the Ashkenazi Jewish population.
abstract: Hoyeraal-Hreidarsson syndrome (HH) is a clinically severe variant of dyskeratosis congenita (DC), characterized by cerebellar hypoplasia, microcephaly, intrauterine growth retardation, and severe immunodeficiency in addition to features of DC. Germline mutations in the RTEL1 gene have recently been identified as causative of HH. In this study, the carrier frequency for five RTEL1 mutations that occurred in individuals of Ashkenazi Jewish descent was investigated in order to advise on including them in existing clinical mutation panels for this population. Our screening showed that the carrier frequency for c.3791G>A (p.R1264H) was higher than expected, 1% in the Ashkenazi Orthodox and 0.45% in the general Ashkenazi Jewish population. Haplotype analyses suggested the presence of a common founder. We recommend that the c.3791G>A RTEL1 mutation be considered for inclusion in carrier screening panels in the Ashkenazi population.
authors.affiliation: Department of Microbiology and Molecular Genetics, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.|Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Fedick
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Shi
authors.affiliation: Bonei Olam, Center for Rare Jewish Genetic Disorders, Brooklyn, NY, USA.
authors.forename: C
authors.identifier: http://orcid.org/0000-0002-3788-0924
authors.initials: C
authors.lastname: Jalas
authors.affiliation: Department of Microbiology and Molecular Genetics, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.|Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Treff
authors.affiliation: Dor Yeshorim, The Committee for Prevention of Jewish Diseases, Brooklyn, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ekstein
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kornreich
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Edelmann
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mehta
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Savage
mesh_terms: D001483:Base Sequence; D004265:DNA Helicases / Q000235:genetics*; D019871:Dyskeratosis Congenita / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis* / Q000235:genetics*; D006580:Genetic Carrier Screening / Q000379:methods*; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D007585:Jews / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C532890:RTEL1 protein, human; D004265:DNA Helicases
keywords: Ashkenazi Jewish; Hoyeraal-Hreidarsson syndrome; RTEL1; carrier screening; dyskeratosis congenita