title: Systematic search for neutropenia should be part of the first screening in patients with poikiloderma.
abstract: Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund-Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia, gingivitis, nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails. Previously undetected and silent neutropenia was evidenced after C16orf57 molecular analysis. Neutropenia was absent in the C16orf57-negative patients. This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis.
authors.affiliation: Centre de Génétique Humaine, CHU Besançon, France. juliette.piard@gmail.com
authors.forename: Juliette
authors.initials: J
authors.lastname: Piard
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Eve
authors.initials: E
authors.lastname: Puzenat
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Jerôme
authors.initials: J
authors.lastname: Franques
authors.forename: Kay
authors.initials: K
authors.lastname: MacDermot
authors.forename: Didier
authors.initials: D
authors.lastname: Bessis
authors.forename: Odile
authors.initials: O
authors.lastname: Boute
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Lucie
authors.initials: L
authors.lastname: Gueneau
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Pierre
authors.initials: P
authors.lastname: Vabres
authors.forename: Benoît
authors.initials: B
authors.lastname: Catteau
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood / Q000235:genetics / Q000473:pathology; D002675:Child, Preschool; D018389:Codon, Nonsense; D003937:Diagnosis, Differential; D004906:Erythrocyte Count; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D009503:Neutropenia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D011038:Rothmund-Thomson Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D018389:Codon, Nonsense; C506731:RECQL4 protein, human; D053484:RecQ Helicases