The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene.

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License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_E8A5E155FB34
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene.
Journal
Genetics in medicine
Author(s)
Peter V.G., Quinodoz M., Pinto-Basto J., Sousa S.B., Di Gioia S.A., Soares G., Ferraz Leal G., Silva E.D., Pescini Gobert R., Miyake N., Matsumoto N., Engle E.C., Unger S., Shapiro F., Superti-Furga A., Rivolta C., Campos-Xavier B.
ISSN
1530-0366 (Electronic)
ISSN-L
1098-3600
Publication state
Published
Issued date
12/2019
Peer-reviewed
Oui
Volume
21
Number
12
Pages
2734-2743
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
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.
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.
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.
Keywords
Adolescent, Adult, Brazil, Carboxy-Lyases/genetics, Carboxy-Lyases/metabolism, Exome/genetics, Female, Genotype, HEK293 Cells, Hearing Loss, Sensorineural/genetics, Humans, Intellectual Disability/genetics, Male, Microcephaly/genetics, Musculoskeletal Abnormalities/genetics, Osteochondrodysplasias/genetics, Pedigree, Phenotype, Portugal, Retinal Degeneration/genetics, Syndrome, Young Adult, Liberfarb syndrome, PISD, phospholipid metabolism, retinal degeneration, skeletal dysplasia
Pubmed
Web of science
Open Access
Yes
Create date
18/07/2019 17:19
Last modification date
15/01/2021 8:12
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