title: Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome.
abstract: De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS.
authors: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan. dslin@ms1.mmh.org.tw
authors: Dar-Shong
authors: DS
authors: Lin
authors: Jui-Hsing
authors: JH
authors: Chang
authors: Hsuan-Liang
authors: HL
authors: Liu
authors: Chin-Hung
authors: CH
authors: Wei
authors: Chun-Yan
authors: CY
authors: Yeung
authors: Che-Sheng
authors: CS
authors: Ho
authors: Chyong-Hsin
authors: CH
authors: Shu
authors: Ming-Fu
authors: MF
authors: Chiang
authors: Chih-Kuang
authors: CK
authors: Chuang
authors: Yu-Wen
authors: YW
authors: Huang
authors: Tsu-Yen
authors: TY
authors: Wu
authors: Yuan-Ren
authors: YR
authors: Jian
authors: Zon-Darr
authors: ZD
authors: Huang
authors: Shuan-Pei
authors: SP
authors: Lin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003318:Corneal Opacity / Q000175:diagnosis / Q000235:genetics*; D003483:Cutis Laxa / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011762:Pyrroline Carboxylate Reductases / Q000235:genetics* / Q000378:metabolism; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase