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Journal of Developmental Biology Sep 2022The expression of the gene is essential for normal skeletal development, affecting both cartilage and bone. Loss of function mutations have been shown to cause...
The expression of the gene is essential for normal skeletal development, affecting both cartilage and bone. Loss of function mutations have been shown to cause abnormalities in the growth plate of long bones, as well as in craniofacial development. However, the specific effects on Meckel's cartilage have not been well studied. To further understand the effect of gene function, we analyzed the developing jaw in zebrafish using gene knockdown by the injection of an antisense morpholino oligonucleotide using transgenic Tg(sp7:EGFP) and Tg(Fli1a:EGFP) EGFP reporter fish, as well as wildtype AB zebrafish. Our results demonstrate that zebrafish knockdown impairs the cellular organization of Meckel's cartilage in the developing jaw and alters the bone formation that occurs adjacent to the Meckel's cartilage. These results suggest roles for Col11a1a protein in cartilage intermediates of bone development, the subsequent mineralization of the bony collar of long bones, and that which occurs adjacent to Meckel's cartilage in the developing jaw.
PubMed: 36278545
DOI: 10.3390/jdb10040040 -
American Journal of Human Genetics Apr 1998Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with...
Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in the COL11A1 gene that cosegregates with the phenotype. The G+1-->A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the major triple-helical domain of the alpha1(XI) collagen polypeptide. The data support the hypothesis that the alpha1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations.
Topics: Chromosomes, Human, Pair 1; Collagen; Craniofacial Abnormalities; Female; Genome, Human; Humans; Male; Mutation; Pedigree; RNA Splicing
PubMed: 9529347
DOI: 10.1086/301789 -
Medicine Nov 2016Recurrent fever syndrome, known as the Marshall syndrome (MS), is a clinical entity that includes several clinical features, such as: fever (39-40°C) that occurs...
BACKGROUND
Recurrent fever syndrome, known as the Marshall syndrome (MS), is a clinical entity that includes several clinical features, such as: fever (39-40°C) that occurs repeatedly at variable intervals (3-8 weeks) and in episodes of 3 to 6 days, cervical adenopathy, pharyngitis, and aphthous stomatitis. The diagnosis of MS is one of exclusions; laboratory data is nonspecific and no abnormalities correlated with MS have been detected thus far.
METHODS
The authors report the case of a 2-year-old girl admitted to a tertiary pediatric center for repeated episodes of fever with aphthous stomatitis and laterocervical adenopathy.
RESULTS
The child's case history raised the suspicion of MS, which was subsequently confirmed by exclusion of all the other differential diagnoses (recurrent tonsillitis, juvenile idiopathic arthritis, Behçet's disease, cyclic neutropenia, hyperglobulinemia D syndrome). After the 3 febrile episodes, bilateral tonsillectomy was performed based on the parents' consent, with favorable immediate and remote postoperative clinical outcomes. The diagnosis of MS is one based on exclusion, as laboratory data is nonspecific. We took into consideration other causes of recurrent fever (recurrent tonsillitis, infectious diseases, juvenile idiopathic arthritis, Behçet's disease, cyclic neutropenia, Familial Mediterranean fever syndrome, hyperglobulinemia D syndrome). In our case, MS criteria were met through clinical examination and the child's outcome. Subsequently, laboratory data helped us establish the MS diagnosis.
CONCLUSIONS
Pediatricians should consider the MS diagnosis in the context of recurrent fever episodes associated with at least one of the following symptoms: pharyngitis, cervical adenopathy or aphthous stomatitis. Despite the indication for tonsillectomy in young children being controversial, in this case the surgery led to the total remission of the disease.
Topics: Cataract; Child, Preschool; Collagen Type XI; Craniofacial Abnormalities; Female; Hearing Loss, Sensorineural; Humans; Osteochondrodysplasias
PubMed: 27858841
DOI: 10.1097/MD.0000000000005065 -
Iranian Journal of Pediatrics Feb 2014Marshall Syndrome or PFAPA is an inflammatory periodic disease characterized by periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Although PFAPA is...
OBJECTIVE
Marshall Syndrome or PFAPA is an inflammatory periodic disease characterized by periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Although PFAPA is an auto inflammatory disease, it doesn't have genetic basis such as other periodic fevers. This study evaluates the 12 common MEFV gene mutations in patients with PFAPA syndrome.
METHODS
21 patients with PFAPA syndrome who had diagnostic criteria were enrolled in this study and 12 common MEFV gene mutations i.e. P369S, F479L, M680I (G/C), M680I (G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H, E148Q evaluated. All the patients were screened for MEFV gene mutations by a reverse hybridization assay (FMF Strip Assay, Vienna lab, Vienna, Austria) according to the instructions provided by the manufacturer. Findings : The age of patients was between 6 months to 14 years, and 15 were males. Seven patients had heterozygote and one had compound heterozygote (K695R, V725A) mutation. There were 4 alleles M694V, 3 alleles V726A, 1 allele E148Q and 1 allele K694R. No significant difference existed between mutated patients with non-mutated in symptoms like aphthous and stomatitis, duration of attacks, episodes of fever and response to treatment. Gaslini score test was not helpful to predict the probability of gene mutations.
CONCLUSION
About 30 percent of patients had MEFV gene mutations but these mutations did not play a main role in presentation of PFAPA symptoms.
PubMed: 25793047
DOI: No ID Found -
Indian Journal of Dermatology,... 2017
Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Cataract; Collagen Type XI; Craniofacial Abnormalities; Hearing Loss, Sensorineural; Humans; Male; Osteochondrodysplasias
PubMed: 28164888
DOI: 10.4103/0378-6323.198447 -
Mammalian Genome : Official Journal of... Aug 2010Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1...
Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed dwarfism and severe ocular defects. The disease phenotype resembles human hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes, although these disorders are usually dominant. Linkage studies mapped drd1 to canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene analysis then led to the identification of a 1-base insertional mutation in exon 1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the 5' end of COL9A2 that cosegregates with drd2. Both mutations affect the COL3 domain of the respective gene. Northern analysis showed that RNA expression of the respective genes was reduced in affected retinas. These models offer potential for studies such as protein-protein interactions between different members of the collagen gene family, regulation and expression of these genes in retina and cartilage, and even opportunities for gene therapy.
Topics: Animals; Animals, Newborn; Arthritis; Base Sequence; Cataract; Collagen Type IX; Collagen Type XI; Connective Tissue Diseases; Craniofacial Abnormalities; Dog Diseases; Dogs; Dwarfism; Eye Diseases, Hereditary; Female; Genes, Recessive; Genetic Association Studies; Hearing Loss, Sensorineural; Humans; Male; Molecular Sequence Data; Mutation; Osteochondrodysplasias; Pedigree; Retinal Detachment
PubMed: 20686772
DOI: 10.1007/s00335-010-9276-4 -
Human Genetics Apr 1998
Topics: Alternative Splicing; Base Composition; Collagen; Humans; Point Mutation; Syndrome
PubMed: 9600252
DOI: 10.1007/s004390050731 -
Cases Journal Oct 2008The Marshall-Stickler phenotype is an autosomal dominant trait comprising ocular abnormalities, sensorineural hearing loss, craniofacial anomalies, and anhidrotic...
BACKGROUND
The Marshall-Stickler phenotype is an autosomal dominant trait comprising ocular abnormalities, sensorineural hearing loss, craniofacial anomalies, and anhidrotic ectodermal dysplasia.
CASE PRESENTATION
A 5-year-old boy from non-consanguineous family in Austria was born with features of Pierre-Robin association (cleft palate, micrognathia, and glossoptosis). Radiological examination at birth revealed coronal clefts of the vertebrae, platyspondyly, and flaring of the metaphyses of the long bones (features suggestive of the Weissenbacher-Zweymuller syndrome). Significant features of ectodermal dysplasia such as sparse hair, defective dentition, dysplastic nails, and deficient sweating associated with bouts of unexplained hyperthermia were present. These features not shared by Stickler syndrome, Wagner syndrome, or Weissenbacher - Zweymuller syndrome, all of which are conditions often confused with Marshall syndrome.
CONCLUSION
There is continuing debate over the clinical overlap and differential diagnosis of Marshall and Stickler syndromes. We compared similar disorders, such as Weissenbacher-Zweymuller, and Wagner syndromes, and conclude that our present patient manifests Marshall-Stickler overlap. Focussing on subtle facial and ectodermal features may detract from recognising the serious outcome of congenital vitreous/myopia anomaly. Retinal detachment with subsequent blindness is a major risk in our current patient.
PubMed: 18950500
DOI: 10.1186/1757-1626-1-270 -
Reumatologia Clinica 2016
Topics: Anti-Inflammatory Agents; Cataract; Child, Preschool; Cholecalciferol; Collagen Type XI; Craniofacial Abnormalities; Disease Progression; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Humans; Osteochondrodysplasias; Prednisolone; Severity of Illness Index; Vitamin D Deficiency; Vitamins
PubMed: 26746599
DOI: 10.1016/j.reuma.2015.11.006 -
BMC Medical Genetics Apr 2013COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome...
BACKGROUND
COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown.
CASE PRESENTATIONS
We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone.
CONCLUSION
Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing.
Topics: Adolescent; Adult; Child, Preschool; Collagen Type XI; Connective Tissue Diseases; Exons; Female; Gene Deletion; Gene Frequency; Humans; Infant; Male; Multiplex Polymerase Chain Reaction; Mutation; RNA Splicing; Sequence Analysis, DNA; Vitreous Detachment
PubMed: 23621912
DOI: 10.1186/1471-2350-14-48