title: Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.
abstract: Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.
authors.affiliation: National Eye Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cukras
authors.forename: Terry
authors.initials: T
authors.lastname: Gaasterland
authors.forename: Pauline
authors.initials: P
authors.lastname: Lee
authors.forename: Harini V
authors.initials: HV
authors.lastname: Gudiseva
authors.forename: Venkata R M
authors.initials: VR
authors.lastname: Chavali
authors.forename: Raghu
authors.initials: R
authors.lastname: Pullakhandam
authors.forename: Bruno
authors.initials: B
authors.lastname: Maranhao
authors.forename: Lee
authors.initials: L
authors.lastname: Edsall
authors.forename: Sandra
authors.initials: S
authors.lastname: Soares
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Radha
authors.initials: R
authors.lastname: Ayyagari
mesh_terms: D000328:Adult; D001483:Base Sequence; D003241:Consanguinity; D002658:Developmental Disabilities / Q000235:genetics*; D004596:Electroretinography; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011228:Prealbumin / Q000378:metabolism; D058499:Retinal Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics* / Q000378:metabolism; D014794:Visual Fields; D014801:Vitamin A / Q000097:blood
chemical_list: D011228:Prealbumin; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A