title: A novel mutation in PYCR1 causes an autosomal recessive cutis laxa with premature aging features in a family.
abstract: The autosomal recessive form of type II cutis laxa (ARCL II) is characterized by the appearance of redundant, inelastic skin with wrinkling, an aged look and additional variable systemic involvement including intrauterine growth retardation, failure to thrive, developmental delay, dysmorphism, osseous abnormality, and CNS manifestations. Several genetic defects have been found in patients and families with the clinical manifestations of ARCL II. Recently, mutations in PYCR1 have been linked to cutis laxa with progeroid features. We ascertained two siblings with of ARCL II born to non-consanguineous parents. Mutation analysis of PYCR1 revealed a novel single-base deletion (c.345delC) in exon 4 leading to frame-shift and premature stop of translation. The effect of this mutation results in a strong reduction of PYCR1 expression in skin fibroblasts from affected siblings. These two cases extend the genotypic spectrum of PYCR1-related ARCL II.
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan. dslin@ms1.mmh.org.tw
authors.forename: Dar-Shong
authors.initials: DS
authors.lastname: Lin
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Yeung
authors.forename: Hsuan-Liang
authors.initials: HL
authors.lastname: Liu
authors.forename: Che-Sheng
authors.initials: CS
authors.lastname: Ho
authors.forename: Chyong-Hsin
authors.initials: CH
authors.lastname: Shu
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chuang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Tsu-Yen
authors.initials: TY
authors.lastname: Wu
authors.forename: Zon-Darr
authors.initials: ZD
authors.lastname: Huang
authors.forename: Yuan-Ren
authors.initials: YR
authors.lastname: Jian
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
mesh_terms: D019588:Aging, Premature / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D003483:Cutis Laxa / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008969:Molecular Sequence Data; D011762:Pyrroline Carboxylate Reductases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase