267 Deep phenotyping of patients with xeroderma pigmentosum and trichothiodystrophy

Abstract

Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) are two rare autosomal recessive diseases that can be caused by mutations in the same XPD (ERCC2) gene, a DNA repair/ transcription helicase. While phenotypically different, XP and TTD both have multi-system clinical abnormalities and increased mortality. XP/TTD overlap patients have features of both diseases. We performed "deep phenotyping" to gain insights into diagnosis and prognosis. We followed a cohort of 68 individuals with defects in the XPD gene (31 XP, 13 XP/TTD, and 24 TTD patients) gathering clinical information from multidisciplinary NIH visits, NIH electronic medical record systems and outside hospital records. For each patient, we assembled 258 clinical and laboratory variables into a database for analysis. We used hierarchical clustering to group the variables and performed a principal component analysis to determine the primary features that distinguish each disease. We found that clustering of variables successfully separated patients by their clinical diagnoses and survival status. We will use principal component analysis with multiple regressions to identify the primary features. Deep phenotyping can identify important phenotypic differences that may improve clinical diagnosis, predict disease prognosis, and guide treatment for patients.