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ELife Aug 2018In historical attempts to treat morning sickness, use of the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their...
In historical attempts to treat morning sickness, use of the drug thalidomide led to the birth of thousands of children with severe birth defects. Despite their teratogenicity, thalidomide and related IMiD drugs are now a mainstay of cancer treatment; however, the molecular basis underlying the pleiotropic biology and characteristic birth defects remains unknown. Here we show that IMiDs disrupt a broad transcriptional network through induced degradation of several CH zinc finger transcription factors, including SALL4, a member of the -like family of developmental transcription factors. Strikingly, heterozygous loss of function mutations in result in a human developmental condition that phenocopies thalidomide-induced birth defects such as absence of thumbs, phocomelia, defects in ear and eye development, and congenital heart disease. We find that thalidomide induces degradation of SALL4 exclusively in humans, primates, and rabbits, but not in rodents or fish, providing a mechanistic link for the species-specific pathogenesis of thalidomide syndrome.
Topics: Abnormalities, Multiple; Adaptor Proteins, Signal Transducing; Amino Acid Sequence; CYS2-HIS2 Zinc Fingers; Duane Retraction Syndrome; Embryonic Stem Cells; HEK293 Cells; Heart Defects, Congenital; Heart Septal Defects, Atrial; Humans; Lower Extremity Deformities, Congenital; Peptide Hydrolases; Phenotype; Protein Binding; Proteolysis; Reproducibility of Results; Species Specificity; Substrate Specificity; Teratogens; Thalidomide; Transcription Factors; Ubiquitin-Protein Ligases; Upper Extremity Deformities, Congenital
PubMed: 30067223
DOI: 10.7554/eLife.38430 -
Journal of Current Ophthalmology Dec 2017Surgical treatment in Duane retraction syndrome (DRS) can be very challenging even for the strabismus specialists because of a wide spectrum of diversity in clinical... (Review)
Review
PURPOSE
Surgical treatment in Duane retraction syndrome (DRS) can be very challenging even for the strabismus specialists because of a wide spectrum of diversity in clinical manifestations. The purpose of this article is to review these different surgical treatments.
METHODS
A comprehensive search was performed using PubMed database with the different keywords of "Duane retraction syndrome" and "surgery". Articles were selected from original English papers published since 2000. The full text of the selected articles was reviewed, and some articles were added based upon the references of the initial articles. We also provided selected case examples about some of these procedures.
RESULTS
125 articles were found in the initial search of which 37 articles were mostly related to the topic of this review. The number finally increased to 59 articles after considering the relative references of the initial articles. Different surgical methods performed on horizontal and vertical rectus muscles (recession, resection, transposition, Y splitting, periosteal fixation and posterior fixation suture) are reviewed. Careful selection of the surgical technique is important to achieve optimal results.
CONCLUSION
With accurate diagnosis of patients with DRS and proper surgical management, several adverse situations associated with this syndrome (amblyopia, abnormal head posture, upshoot, downshoot, and muscle underaction) can be prevented.
PubMed: 29270470
DOI: 10.1016/j.joco.2017.08.008 -
Molecular Medicine Reports Apr 2022Okihiro syndrome is an autosomal dominant condition characterized by Duane anomaly and radial ray defects. The present study aimed to analyze the clinical manifestations...
Okihiro syndrome is an autosomal dominant condition characterized by Duane anomaly and radial ray defects. The present study aimed to analyze the clinical manifestations of a patient with Okihiro syndrome and perform genetic testing on the proband and his family to determine the biological pathogenesis. Clinical data were collected from the proband and his family and genomic DNA was extracted from peripheral blood. Whole exome sequencing was performed by high‑throughput sequencing and mutation sites of the proband and his parents were validated by Sanger sequencing. The proband was diagnosed with Okihiro syndrome, which is characterized by bone abnormality in the arms and hands (radial ray malformation, absence of thumbs) and sensorineural hearing loss. A pathogenic heterozygous c.3060delG variant was identified in exon 4 of spalt‑like transcription factor 4 () gene in the proband. This is a frameshift mutation that changes increases the length of SALL4 protein from 1,053 to 1,076 amino acids. The variant was classed as a mutation because the parents of the proband showed no variation at this site. This variant is not included in the ClinVar database and, to the best of our knowledge, has not previously been reported. The heterozygous c.3060delG variant was the molecular pathological cause of Okihiro syndrome in the present study and expanded the database of known variants.
Topics: China; Duane Retraction Syndrome; Heterozygote; Humans; Mutation; Pedigree; Transcription Factors
PubMed: 35179219
DOI: 10.3892/mmr.2022.12647 -
Indian Journal of Ophthalmology Aug 2014
Topics: Accommodation, Ocular; Duane Retraction Syndrome; Esotropia; Eye Movements; Female; Humans; Male; Oculomotor Muscles; Ophthalmologic Surgical Procedures; Vision, Binocular
PubMed: 25360471
DOI: 10.4103/0301-4738.141070 -
Journal of Current Ophthalmology 2021To provide a comprehensive review on different characteristics of abnormal head postures (AHPs) due to different ocular causes, its measurement, and its effect on facial... (Review)
Review
PURPOSE
To provide a comprehensive review on different characteristics of abnormal head postures (AHPs) due to different ocular causes, its measurement, and its effect on facial appearance.
METHODS
In this review article, PubMed, Scopus, and Google Scholar search engines were searched for the scientific articles and books published between 1975 and September 2020 based on the keywords of this article. The selected articles were collected, summarized, classified, evaluated, and finally concluded.
RESULTS
AHP can be caused by various ocular or nonocular diseases. The prevalence of ocular causes of AHP was reported to be 18%-25%. 1.1% of patients presenting to ophthalmology clinics has AHP. The first step in evaluating a patient with AHP is a correct differential diagnosis between nonocular and ocular sources by performing comprehensive eye examinations and ruling out other causes of orthopedic and neurological AHP. Ocular AHP occurs for a variety of reasons, the most important of which include nystagmus, superior oblique palsy, and Duane's retraction syndrome. AHP may be an essential clinical sign for an underlying disease, which can only be appropriately treated by the accurate determination of the cause. Long-standing AHP may lead to facial asymmetry and secondary muscular and skeletal changes.
CONCLUSION
In conclusion, a proper differential diagnosis between nonocular and ocular causes, knowledge of the different forms of AHP and their measurement methods, accurate diagnosis of the cause, and proper and timely treatment of ocular AHP can prevent facial asymmetry and secondary muscular and skeletal changes in the patients.
PubMed: 35128182
DOI: 10.4103/joco.joco_114_20 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Abduction limitation in esotropic Duane retraction syndrome (DRS), esotropic Mobius syndrome, and sixth nerve palsy is one of the difficult-to-manage problems in... (Review)
Review
Abduction limitation in esotropic Duane retraction syndrome (DRS), esotropic Mobius syndrome, and sixth nerve palsy is one of the difficult-to-manage problems in strabismus surgery. The procedure of superior rectus transposition (SRT) was introduced by Johnston et al. In this procedure, the superior rectus (SR) muscle is disinserted and sutured adjacent to the insertion of lateral rectus (LR) muscle. The purpose of this review is to explore literature about efficacy and safety of SRT and its usage in strabismus surgery.
PubMed: 36444206
DOI: 10.2147/OPTH.S359313