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The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene.
Peter, Virginie G; Quinodoz, Mathieu; Pinto-Basto, Jorge; Sousa, Sergio B; Di Gioia, Silvio Alessandro; Soares, Gabriela; Ferraz Leal, Gabriela; Silva, Eduardo D; Pescini Gobert, Rosanna; Miyake, Noriko; Matsumoto, Naomichi; Engle, Elizabeth C; Unger, Sheila; Shapiro, Frederic; Superti-Furga, Andrea; Rivolta, Carlo; Campos-Xavier, Belinda.
Afiliação
  • Peter VG; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Quinodoz M; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
  • Pinto-Basto J; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Sousa SB; Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
  • Di Gioia SA; CGC Genetics, Porto, Portugal.
  • Soares G; Medical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
  • Ferraz Leal G; University Clinic of Genetics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
  • Silva ED; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • Pescini Gobert R; Center for Medical Genetics Dr. Jacinto Magalhães, Porto Hospital Center, Porto, Portugal.
  • Miyake N; Fernando Figueira Integral Medicine Institute, Recife, Brazil.
  • Matsumoto N; Medical Genetics Unit, University of Pernambuco, Recife, Brazil.
  • Engle EC; Centro Cirúrgico de Coimbra, Coimbra, Portugal.
  • Unger S; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
  • Shapiro F; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Superti-Furga A; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
  • Rivolta C; Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • Campos-Xavier B; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Genet Med ; 21(12): 2734-2743, 2019 12.
Article em En | MEDLINE | ID: mdl-31263216
PURPOSE: We observed four individuals in two unrelated but consanguineous families from Portugal and Brazil affected by early-onset retinal degeneration, sensorineural hearing loss, microcephaly, intellectual disability, and skeletal dysplasia with scoliosis and short stature. The phenotype precisely matched that of an individual of Azorean descent published in 1986 by Liberfarb and coworkers. METHODS: Patients underwent specialized clinical examinations (including ophthalmological, audiological, orthopedic, radiological, and developmental assessment). Exome and targeted sequencing was performed on selected individuals. Minigene constructs were assessed by quantitative polymerase chain reaction (qPCR) and Sanger sequencing. RESULTS: Affected individuals shared a 3.36-Mb region of autozygosity on chromosome 22q12.2, including a 10-bp deletion (NM_014338.3:c.904-12_904-3delCTATCACCAC), immediately upstream of the last exon of the PISD (phosphatidylserine decarboxylase) gene. Sequencing of PISD from paraffin-embedded tissue from the 1986 case revealed the identical homozygous variant. In HEK293T cells, this variant led to aberrant splicing of PISD transcripts. CONCLUSION: We have identified the genetic etiology of the Liberfarb syndrome, affecting brain, eye, ear, bone, and connective tissue. Our work documents the migration of a rare Portuguese founder variant to two continents and highlights the link between phospholipid metabolism and bone formation, sensory defects, and cerebral development, while raising the possibility of therapeutic phospholipid replacement.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carboxiliases Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Female / Humans / Male País/Região como assunto: America do sul / Brasil / Europa Idioma: En Revista: Genet Med Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carboxiliases Tipo de estudo: Prognostic_studies Limite: Adolescent / Adult / Female / Humans / Male País/Região como assunto: America do sul / Brasil / Europa Idioma: En Revista: Genet Med Assunto da revista: GENETICA MEDICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suíça País de publicação: Estados Unidos