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Journal of Developmental Biology Aug 2020The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and...
The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in . Zebrafish carry two copies of the gene, designated and . is located on zebrafish chromosome 24 and is located on zebrafish chromosome 2. Expression patterns are distinct for and and is most similar to that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse model . We investigated the function of in craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel's cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene for is required for normal development and has similar functions to the mammalian gene. Due to its transparency, external fertilization, the knockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understand -related early developmental events.
PubMed: 32872105
DOI: 10.3390/jdb8030016 -
Annals of Human Genetics Sep 2020We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation...
We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.
Topics: Adolescent; Adult; Arthritis; Child; Child, Preschool; Collagen Type II; Collagen Type XI; Connective Tissue Diseases; Czech Republic; DNA Mutational Analysis; Female; Hearing Loss, Sensorineural; Humans; Infant; Male; Middle Aged; Pedigree; Phenotype; Retinal Detachment; Young Adult
PubMed: 32427345
DOI: 10.1111/ahg.12386 -
Journal of Cutaneous Pathology Feb 2020Sweet syndrome is rare in the pediatric population and usually responds well to treatment, resolving without sequelae. Marshall syndrome is a rare pediatric skin disease...
Sweet syndrome is rare in the pediatric population and usually responds well to treatment, resolving without sequelae. Marshall syndrome is a rare pediatric skin disease characterized by loss of elastic tissue (cutis laxa) secondary to acquired, localized neutrophilic dermatitis without any internal organ involvement. Only few cases of Marshall syndrome (acquired cutis laxa type II) have been reported. Systemic steroids and dapsone show excellent results in Sweet syndrome. Although there is no satisfactory treatment for cutis laxa, dapsone can be used in the acute phase for control of swelling.
Topics: Cataract; Child, Preschool; Collagen Type XI; Craniofacial Abnormalities; Cutis Laxa; Dapsone; Female; Hearing Loss, Sensorineural; Humans; Osteochondrodysplasias; Sweet Syndrome
PubMed: 31437319
DOI: 10.1111/cup.13567