title: Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund-Thomson/Baller-Gerold syndromes.
abstract: Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type poikiloderma with neutropenia, hereditary sclerosing poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma.
authors.affiliation: EA 4271 GAD "Génétique des Anomalies du Développement", IFR Santé STIC, Université de Bourgogne, Dijon, France; Centre de Génétique Humaine, CHU Besançon, Besançon, France.
authors.forename: J
authors.initials: J
authors.lastname: Piard
authors.forename: B
authors.initials: B
authors.lastname: Aral
authors.forename: P
authors.initials: P
authors.lastname: Vabres
authors.forename: M
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: A
authors.initials: A
authors.lastname: Mégarbané
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: V
authors.initials: V
authors.lastname: Capra
authors.forename: G
authors.initials: G
authors.lastname: Pierquin
authors.forename: P
authors.initials: P
authors.lastname: Callier
authors.forename: C
authors.initials: C
authors.lastname: Baumann
authors.forename: L
authors.initials: L
authors.lastname: Pasquier
authors.forename: G
authors.initials: G
authors.lastname: Baujat
authors.forename: L
authors.initials: L
authors.lastname: Martorell
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez
authors.forename: A F
authors.initials: AF
authors.lastname: Brady
authors.forename: F
authors.initials: F
authors.lastname: Boralevi
authors.forename: M A
authors.initials: MA
authors.lastname: González-Enseñat
authors.forename: M
authors.initials: M
authors.lastname: Rio
authors.forename: C
authors.initials: C
authors.lastname: Bodemer
authors.forename: N
authors.initials: N
authors.lastname: Philip
authors.forename: M-P
authors.initials: MP
authors.lastname: Cordier
authors.forename: A
authors.initials: A
authors.lastname: Goldenberg
authors.forename: B
authors.initials: B
authors.lastname: Demeer
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: E
authors.initials: E
authors.lastname: Blair
authors.forename: E
authors.initials: E
authors.lastname: Puzenat
authors.forename: P
authors.initials: P
authors.lastname: Parent
authors.forename: Y
authors.initials: Y
authors.lastname: Sznajer
authors.forename: C
authors.initials: C
authors.lastname: Francannet
authors.forename: N
authors.initials: N
authors.lastname: DiDonato
authors.forename: O
authors.initials: O
authors.lastname: Boute
authors.forename: V
authors.initials: V
authors.lastname: Barlogis
authors.forename: O
authors.initials: O
authors.lastname: Moldovan
authors.forename: D
authors.initials: D
authors.lastname: Bessis
authors.forename: C
authors.initials: C
authors.lastname: Coubes
authors.forename: M
authors.initials: M
authors.lastname: Tardieu
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: A B
authors.initials: AB
authors.lastname: Sousa
authors.forename: J
authors.initials: J
authors.lastname: Franques
authors.forename: A
authors.initials: A
authors.lastname: Toutain
authors.forename: M
authors.initials: M
authors.lastname: Tajir
authors.forename: S C
authors.initials: SC
authors.lastname: Elalaoui
authors.forename: D
authors.initials: D
authors.lastname: Geneviève
authors.forename: J
authors.initials: J
authors.lastname: Thevenon
authors.forename: J-B
authors.initials: JB
authors.lastname: Courcet
authors.forename: J-B
authors.initials: JB
authors.lastname: Rivière
authors.forename: C
authors.initials: C
authors.lastname: Collet
authors.forename: N
authors.initials: N
authors.lastname: Gigot
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D011884:Radius / Q000002:abnormalities*; D053484:RecQ Helicases / Q000235:genetics*; D055815:Young Adult
chemical_list: C506731:RECQL4 protein, human; D053484:RecQ Helicases
keywords: Baller-Gerold syndrome; RECQL4; Rothmund-Thomson syndrome; poikiloderma