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Exome Sequencing Reveals Mutations in AIRE as a Cause of Isolated Hypoparathyroidism.
Li, Dong; Streeten, Elizabeth A; Chan, Alice; Lwin, Wint; Tian, Lifeng; Pellegrino da Silva, Renata; Kim, Cecilia E; Anderson, Mark S; Hakonarson, Hakon; Levine, Michael A.
Afiliación
  • Li D; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
  • Streeten EA; Division of Endocrinology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
  • Chan A; Division of Diabetes, University of Maryland School of Medicine, Baltimore, Maryland 21201.
  • Lwin W; Division of Nutrition and Genetics, University of Maryland School of Medicine, Baltimore, Maryland 21201.
  • Tian L; Department of Pediatrics, University of California-San Francisco, San Francisco, California 94143.
  • Pellegrino da Silva R; Diabetes Center, University of California-San Francisco, San Francisco, California 94143.
  • Kim CE; Department of Medicine, University of California-San Francisco, San Francisco, California 94143.
  • Anderson MS; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
  • Hakonarson H; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
  • Levine MA; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
J Clin Endocrinol Metab ; 102(5): 1726-1733, 2017 05 01.
Article en En | MEDLINE | ID: mdl-28323927
Context: Most cases of autosomal recessive hypoparathyroidism (HYPO) are caused by loss-of-function mutations in GCM2 or PTH. Objective: The objective of this study was to identify the underlying genetic basis for isolated HYPO in a kindred in which 3 of 10 siblings were affected. Subjects: We studied the parents and the three adult affected subjects, each of whom was diagnosed with HYPO in the first decade of life. Methods: We collected clinical and biochemical data and performed whole exome sequencing analysis on DNA from the three affected subjects after negative genetic testing for known causes of HYPO. Results: Whole exome sequencing followed by Sanger sequencing revealed that all three affected subjects were compound heterozygous for two previously reported mutations, c.967_979delCTGTCCCCTCCGC:p.(L323SfsX51) and c.995+(3_5)delGAGinsTAT, in AIRE, which encodes the autoimmune regulator protein that is defective in autoimmune polyglandular syndrome type 1 (APS-1). Each parent carries one mutation, and all of the children of the patients are either heterozygous for one mutation or wild type. The affected sister developed premature ovarian failure, but the two affected brothers have no other features of APS-1 despite elevated serum levels of anti-interferon-α antibodies. Conclusions: Our findings indicate that biallelic mutations in AIRE can cause isolated HYPO as well as syndromic APS-1. The presence of antibodies to interferon-α provides a highly sensitive indicator for loss of AIRE function and represents a useful marker for isolated HYPO due to AIRE mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Insuficiencia Ovárica Primaria / Hipoparatiroidismo Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Insuficiencia Ovárica Primaria / Hipoparatiroidismo Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Clin Endocrinol Metab Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos