title: The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2.
abstract: Geroderma osteodysplasticum is a rare autosomal recessive disorder characterized by wrinkled skin on the dorsum of the hands and feet, osteopenia, prognathism, and an elongated and lax face. The mutated gene was identified as GORAB (SCYL1BP1). As well, the PYCR1 gene also was shown to be mutated in a similar disease, designated cutis laxa, autosomal recessive, type IIB (ARCL2B) or cutis laxa with progeroid features. We describe here the clinical findings in four affected individuals in a family with geroderma osteodysplasticum with mental retardation and a homozygous mutation in PYCR1. Although the disease resulting from recessive mutations in that gene has been recently designated ARCL2B, some clinical features, such as prognathism, elongated and lax face, osteopenia and limitation of skin wrinkling to the dorsum of hands and feet, in the patients reported here as well as in others reported with PYCR1 mutations, are generally more common in geroderma osteodysplasticum resulting from recessive GORAB mutations. While the patients with GORAB mutations have severe osteopenia, the patients with PYCR1 mutations have severe mental retardation. In conclusion, the phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than ARCL2B.
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul, Turkey.
authors.forename: Yeşerin
authors.initials: Y
authors.lastname: Yildirim
authors.forename: Aslihan
authors.initials: A
authors.lastname: Tolun
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D001847:Bone Diseases / Q000151:congenital / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004392:Dwarfism / Q000235:genetics / Q000473:pathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D000077614:Golgi Matrix Proteins; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011762:Pyrroline Carboxylate Reductases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000473:pathology; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D000077614:Golgi Matrix Proteins; D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase; C533680:GORAB protein, human