Titre
The Liberfarb syndrome, a multisystem disorder affecting eye, ear, bone, and brain development, is caused by a founder pathogenic variant in thePISD gene.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Peter, V.G.
Auteure/Auteur
Quinodoz, M.
Auteure/Auteur
Pinto-Basto, J.
Auteure/Auteur
Sousa, S.B.
Auteure/Auteur
Di Gioia, S.A.
Auteure/Auteur
Soares, G.
Auteure/Auteur
Ferraz Leal, G.
Auteure/Auteur
Silva, E.D.
Auteure/Auteur
Pescini Gobert, R.
Auteure/Auteur
Miyake, N.
Auteure/Auteur
Matsumoto, N.
Auteure/Auteur
Engle, E.C.
Auteure/Auteur
Unger, S.
Auteure/Auteur
Shapiro, F.
Auteure/Auteur
Superti-Furga, A.
Auteure/Auteur
Rivolta, C.
Auteure/Auteur
Campos-Xavier, B.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1530-0366
Statut éditorial
Publié
Date de publication
2019-12
Volume
21
Numéro
12
Première page
2734
Dernière page/numéro d’article
2743
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
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.
Sujets
PID Serval
serval:BIB_E8A5E155FB34
PMID
Open Access
Oui
Date de création
2019-07-18T15:19:19.351Z
Date de création dans IRIS
2025-05-21T05:31:40Z
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Nom
31263216_BIB_E8A5E155FB34.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
1.55 MB
Format
Adobe PDF
PID Serval
serval:BIB_E8A5E155FB34.P001
URN
urn:nbn:ch:serval-BIB_E8A5E155FB342
Somme de contrôle
(MD5):962619402bad3c549676a1c5c6253268