P21 Bi-allelic TUFT1 variants in two siblings with woolly hair and skin fragility

Abstract

Abstract TUFT1 encodes tuftelin-1, a glycoprotein thought to play a major role in mineralization and structural organization of enamel, but it has not been implicated in any monogenic enamel disorders. Recently, Jackson et al. (2023) identified that tuftelin-1 has a role in desmosomal function. Pathology in desmosomal components causes disorders affecting the skin, hair, and heart. Newly described bi-allelic loss-of-function TUFT1 variants (OMIM600087) cause a novel skin fragility-woolly hair phenotype. We present two siblings from non-consanguineous parents of Irish and British ancestry. Both had normal skin at birth and developed widespread blisters on day two of life, on the limbs, buttocks area and inside the mouth. Although their skin fragility had improved with age, they still developed flare-ups with multiple small blisters, mainly on their limbs when viral illness. They had mild palmoplantar keratoderma and skin peeling. Their most characteristic phenotype was slow-­growing woolly hair that did not need cutting until the age of 5 years old in the older sibling. The eyebrows and eyelashes were unaffected. Recently, the older sibling has developed keratosis pilaris on her arms. The heart was unaffected with normal electrocardiogram and echocardiogram. Whole exome sequencing identified homozygous NM_020127:c.60+1G>A TUFT1 variants in both affected individuals. These two cases reflect a novel condition. The predominant clinical phenotype is woolly hair and early signs of skin fragility. Despite having a role in desmosomal integrity bi-­allelic loss-of-function TUFT1 variants do not appear to cause cardiac pathology.