Family with Two Rare Syndromes Reveals Immunity Glitch

Members of a three-generation family in France who suffer from widespread infections and fragile skin, joints, bones, and blood vessels share an underlying and unexpected immune system glitch, according to a new report in Science Immunology.

The grandmother died of septic shock at age 76. She had the same collection of problems that plague her 45-year-old daughter, and her 19-year-old granddaughter. They have two syndromes that aren’t known to occur together:

  • “Chronic mucocutaneous candidiasis” brings persistent infections with the yeast Candida albicans, in the vagina, skin folds, mouth (thrush), and other mucosal linings. All three women also suffer UTIs, ear-nose-and-throat infections, and bacterial skin infections.
  • Connective tissue disorders similar to Ehlers-Danlos syndrome include hypermobile joints; soft, velvety, super-stretchy skin; palm and sole blisters; stretch marks; slow wound healing; poor digestion; osteoporosis; and, most debilitating, chronic widespread pain. Abnormal connective tissue is dangerous, because blood vessels and organs such as the uterus and intestines can burst.

Yet other symptoms include frequent migraines, fatigue, insomnia, Reynaud’s phenomenon, tumors, and retained baby teeth.

The women treat the symptoms one-at-a-time: rounds of antibiotics, painkillers, digestive aids, skin creams, vitamin D supplements, osteoporosis drugs, and more. But what if a single mutation lay behind the spectrum of symptoms? Would identifying it reveal a single drug target that could make their lives easier – either a repurposed drug or impetus to develop a new one? Dissecting the cell-cell signaling pathways gone off course might lead to novel therapeutic approaches to either of the two arrays of symptoms, helping others.

The information on this intriguing family is part of a resource called the human gene connectome, developed at the St. Giles Laboratory of Human Genetics of Infectious Diseases at Rockefeller University. Led by Jean-Laurent Casanova and with international collaborators, the group is illuminating how single-gene mutations spotlight immune system problems. In my 2013 post “A GPS View of the Human Genome,”  team member Yuval Itan explained how the connectome works.

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