Fig. 2

TYMP homozygous pathogenic variant in a newly-characterized lipoatrophic diabetes. A Genealogical trees and segregation analysis for the TYMP variants in the two families investigated herein. Arrows indicate probands. +, normal allele; M, mutant allele. B Top panel: schematic representation of TYMP genomic sequence displaying the location of the variants identified. Bottom panel: schematic representation of thymidine phosphorylase (TP) protein sequence comprising 482 amino acids. The prediction of protein domain organization was based on UniProt database (protein reference: P19971). C Left panel: Schematic drawing showing the functional impact of TYMP pathogenic variants. Right panel: Biochemical measurement of TP activity in family A (patients 1 and 2, and their two parents). The enzyme activity was evaluated by an endpoint determination of the thymine formed after 1 h incubation of leukocytes in the presence of an excess of its thymidine substrate