ArticleAmerican journal of human genetics2013
Recessive and dominant mutations in retinoic acid receptor beta in cases with microphthalmia and diaphragmatic hernia.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 111 citations in OpenAlex.
- Characterization of Ocular Developmental Disorders in the Israeli Population: Genotype-Phenotype Correlations and Novel Candidate Genes.Biomolecules · 2026Article
- Clinical features of syndromic microphthalmia in two novel RARB variants.Human genome variation · 2026Article
- Genetic architecture and prognostic significance of suspected fetal microcephaly: evidence from prenatal exome sequencing in a large prospective cohort.Human genomics · 2026Article
- Novel Variant of RARB Gene in Familial Isolated Ocular Coloboma: A Case Report.The American journal of case reports · 2025Article
- Unilateral Lung Agenesis: A Systematic Review of Prevalence, Anatomical Variants, and Clinical Implications.Diagnostics (Basel, Switzerland) · 2025Review
- Integrative single-cell atlas unveils heterogeneity and prognostic value of cancer-associated fibroblasts in gastric cancer.Frontiers in oncology · 2025Article
- Report of one case with de novo mutation in TLK2 and literature review.BMC pediatrics · 2024Review
- Osteopetrosis-like disorders induced by osteoblast-specific retinoic acid signaling inhibition in mice.Bone research · 2024Article
- Matthew-Wood Syndrome in Monochorionic, Diamnionic Twins.Journal of pediatric genetics · 2024Article
- The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later.Pediatric research · 2024Review
- AHuman mutation · 2024Article
- Role of genetics and the environment in the etiology of congenital diaphragmatic hernia.World journal of pediatric surgery · 2024Review
- Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Copy number variations analysis in a cohort of 47 fetuses and newborns with congenital diaphragmatic hernia.Prenatal diagnosis · 2022Article
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.American journal of medical genetics. Part A · 2022Article
- The role of exome sequencing in childhood interstitial or diffuse lung disease.Orphanet journal of rare diseases · 2022Article
- Underlying genetic etiologies of congenital diaphragmatic hernia.Prenatal diagnosis · 2022Review
- All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.PloS one · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
Anophthalmia and/or microphthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac defects are the main features of PDAC syndrome. Recessive mutations in STRA6, encoding a membrane receptor for the retinol-binding protein, have been identified in some cases with PDAC syndrome, although many cases have remained unexplained. Using whole-exome sequencing, we found that two PDAC-syndrome-affected siblings, but not their unaffected sibling, were compound heterozygous for nonsense (c.355C>T [p.Arg119(∗)]) and frameshift (c.1201_1202insCT [p.Ile403Serfs(∗)15]) mutations in retinoic acid receptor beta (RARB). Transfection studies showed that p.Arg119(∗) and p.Ile403Serfs(∗)15 altered RARB had no transcriptional activity in response to ligands, confirming that the mutations induced a loss of function. We then sequenced RARB in 15 subjects with anophthalmia and/or microphthalmia and at least one other feature of PDAC syndrome. Surprisingly, three unrelated subjects with microphthalmia and diaphragmatic hernia showed de novo missense mutations affecting the same codon; two of the subjects had the c.1159C>T (Arg387Cys) mutation, whereas the other one carried the c.1159C>A (p.Arg387Ser) mutation. We found that compared to the wild-type receptor, p.Arg387Ser and p.Arg387Cys altered RARB induced a 2- to 3-fold increase in transcriptional activity in response to retinoic acid ligands, suggesting a gain-of-function mechanism. Our study thus suggests that both recessive and dominant mutations in RARB cause anophthalmia and/or microphthalmia and diaphragmatic hernia, providing further evidence of the crucial role of the retinoic acid pathway during eye development and organogenesis.
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