AUTHOR=Martins Davi Jardim , Di Lazzaro Filho Ricardo , Bertola Debora Romeo , Hoch Nícolas Carlos 

TITLE=Rothmund-Thomson syndrome, a disorder far from solved

JOURNAL=Frontiers in Aging

VOLUME=4

YEAR=2023

URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2023.1296409

DOI=10.3389/fragi.2023.1296409

ISSN=2673-6217

ABSTRACT=<p>Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a range of clinical symptoms, including poikiloderma, juvenile cataracts, short stature, sparse hair, eyebrows/eyelashes, nail dysplasia, and skeletal abnormalities. While classically associated with mutations in the <italic>RECQL4</italic> gene, which encodes a DNA helicase involved in DNA replication and repair, three additional genes have been recently identified in RTS: <italic>ANAPC1</italic>, encoding a subunit of the APC/C complex; <italic>DNA2,</italic> which encodes a nuclease/helicase involved in DNA repair; and <italic>CRIPT</italic>, encoding a poorly characterized protein implicated in excitatory synapse formation and splicing. Here, we review the clinical spectrum of RTS patients, analyze the genetic basis of the disease, and discuss molecular functions of the affected genes, drawing some novel genotype-phenotype correlations and proposing avenues for future studies into this enigmatic disorder.</p>