title: Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome.
abstract: Unbiased genetic diagnosis has increasingly associated seemingly unrelated somatic and immunological phenotypes. We report a male infant who presented within the first year of life with physical growth impairment, feeding difficulties, hyperemesis without diarrhea, and abnormal hair findings suggestive of trichorrhexis nodosa. With advancing age, moderate global developmental delay, susceptibility to frequent viral illnesses, otitis media, and purulent conjunctivitis were identified. Because of the repeated infections, an immunological evaluation was pursued and identified impaired antibody memory responses following pneumococcal vaccine administration. Immunoglobulin replacement therapy and nutritional support were employed as mainstays of therapy. The child is now aged 12 years and still without diarrhea. Whole exome sequencing identified compound heterozygous mutations in the TTC37 gene, a known cause of the trichohepatoenteric syndrome (THES). This case extends the known phenotype of THES and defines a potential subset for inclusion as an immune overlap syndrome.
authors: Department of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital , Houston, TX , USA.
authors: Nicholas L
authors: NL
authors: Rider
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University , New York, NY , USA.
authors: Bertrand
authors: B
authors: Boisson
authors: Department of Allergy-Immunology, The Children's Hospital of Philadelphia , Philadelphia, PA , USA.
authors: Soma
authors: S
authors: Jyonouchi
authors: Immunodeficiency and Inflammation Unit, National Institute of Arthritis, Musculoskeletal and Skin Disease, National Institutes of Health , Bethesda, MD , USA.
authors: Eric P
authors: EP
authors: Hanson
authors: Laboratory of Host Defense, National Institute of Allergy and Infectious Disease, National Institutes of Health , Bethesda, MD , USA.
authors: Sergio D
authors: SD
authors: Rosenzweig
authors: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University , New York, NY , USA ; Necker Hospital for Sick Children, Imagine Institute, INSERM, HHMI, Paris Descartes University , Paris , France ; Howard Hughes Medical Institute , New York, NY , USA.
authors: Jean-Laurent
authors: JL
authors: Cassanova
authors: Department of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital , Houston, TX , USA.
authors: Jordan S
authors: JS
authors: Orange
keywords: antibody deficiency; chronic diarrhea; ectodermal dysplasia; primary immunodeficiency; trichohepatoenteric syndrome; trichorrhexis nodosa