Developing Del2Phen: A Novel Phenotype Description Tool for Chromosome Deletions

Information on the health-related consequences of rare chromosome disorders is often limited, posing challenges for both patients and their families. The Chromosome 6 Project aims to bridge this knowledge gap for structural aberrations involving chromosome 6 by providing parents of affected children with information on the expected phenotypes of their child. To achieve this, detailed phenotype and genotype data are collected directly from parents worldwide and supplemented with data from literature reports, resulting thus far in a dataset of over 500 individuals. This comprehensive data pool was used to develop Del2Phen, a software tool introduced in this paper that generates aberration-specific phenotype information for chromosome disorders. Del2Phen identifies individuals with a deletion or duplication similar to that of a new patient (index) and produces a clinical description for the index based on phenotypic features observed in these genotypically similar individuals. Genotypic similarity is determined using existing knowledge on the haploinsufficiency effect of genes and established gene-phenotype relationships. The optimal genotypic similarity parameters for chromosome 6 deletions were evaluated, which led to thorough and reliable clinical descriptions based on sufficiently large groups of individuals with highly similar deletions. Although currently optimised for chromosome 6 deletions, Del2Phen can also be applied to deletions involving other chromosomes and is easily adapted for use on duplications, given sufficient data are available. Del2Phen can already be used to expedite data analysis for chromosome disorders, thus aiding healthcare professionals in delivering appropriate clinical care. Lastly, this tool will be integrated into an interactive website designed for parents of children with a chromosome 6 aberration, providing essential health information in a timely and accessible manner.