title: A patient with Baller-Gerold syndrome and midline NK/T lymphoma.
abstract: Three autosomal recessive disorders are associated with mutations in the RECQL4 gene: Rothmund-Thomson syndrome (RTS), Baller-Gerold syndrome (BGS), and RAPADILINO syndrome. BGS is characterized by two major clinical abnormalities: craniosynostosis and preaxial limb anomalies but not cancer development. We performed RECQL4 mutation detection in a patient with BGS and several clinical signs of RTS who developed a midline NK/T-cell lymphoma. Sequencing was used to identify RECQL4 mutations, and RNA analysis was used to examine expression of mRNA in leukocytes. The patient was found to be compound heterozygous for two mutations in exon 15, namely c.[2492_2493delAT] + c.[2506_2518del13bp]. We found that only the allele with 13 bp deletion was expressed in blood leukocytes. Our patient showed severe phenotypic abnormalities, with clinical signs of both BGS and RTS. She developed an extranodal NK/T-cell lymphoma, which is extremely rare in children of her age and is the first described case of BGS with development of a cancer. This case of a RECQL4-related disorder highlights the significant phenotypic overlap between the classically delineated RECQL4-associated syndromes and questions the need to redefine or combine these clinical entities.
authors.affiliation: Center for Medical Genetics, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
authors.forename: Marusa
authors.initials: M
authors.lastname: Debeljak
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Zver
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D003398:Craniosynostoses / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D053484:RecQ Helicases / Q000235:genetics*; D011038:Rothmund-Thomson Syndrome / Q000235:genetics; D017384:Sequence Deletion; D013577:Syndrome; D051879:Twist-Related Protein 1 / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C506731:RECQL4 protein, human; D053484:RecQ Helicases