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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 -
American Journal of Medical Genetics.... Apr 2024Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of <1 in 1 million. Based on the literature reviewed, this is the...
Marshall syndrome is an extremely rare genetic disorder usually diagnosed in infancy with a prevalence of <1 in 1 million. Based on the literature reviewed, this is the first case report to provide a longitudinal history of a child with Marshall syndrome (from birth to age 12.5 years). This longitudinal case report arose in part from desires of this child's parents to share the story of their early fears at her initial diagnosis and compare those to how well she has turned out.
Topics: Humans; Child; Female; Mutation; Osteochondrodysplasias; Craniofacial Abnormalities; Hearing Loss, Sensorineural; Syndrome; Cataract; Collagen Type XI
PubMed: 38062645
DOI: 10.1002/ajmg.a.63488 -
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 -
Vestnik Oftalmologii 2024Degenerative changes in the peripheral regions of the ocular fundus allow a closer look at both the role of collagen genes and their mutations in children with high...
UNLABELLED
Degenerative changes in the peripheral regions of the ocular fundus allow a closer look at both the role of collagen genes and their mutations in children with high myopia.
PURPOSE
The study investigates the features of genetic mutations in children with high myopia combined with peripheral retinal degenerations.
MATERIAL AND METHODS
Study group was formed from the database of genetic studies of the Scientific and Clinical Center OOO Oftalmic, which consists of 4362 patients referred for medical genetic counseling and molecular genetic testing from 2016 to 2021. Selection criteria were: male and female patients, aged 5-18 years old, who had the following clinical signs: high myopia (>6.00 D) and the presence of peripheral retinal degenerations (PRD). The study considered both isolated cases of ophthalmic pathology, as well as its syndromic forms. The final selection included 40 children. All patients had consulted with a geneticist. Whole-exome sequencing (WES), next generation sequencing (NGS), and single gene sequencing were conducted by taking 5 mL of peripheral venous blood and extracting deoxyribonucleic acid (DNA).
RESULTS
In patients with isolated cases of ophthalmic pathology (peripheral retinal degenerations and high myopia) with a confirmed genetic diagnosis, mutations in the gene were detected in 77.4% of cases, and in the gene - in 22.6% of cases. In Stickler syndrome with a confirmed genetic diagnosis, mutations in the gene were detected in 33.3% of cases. In Marshall syndrome, the mutation in the gene was detected in 11.1% of cases. In children with Ehlers-Danlos, Knobloch type 1, Cohen, Marfan, Wagner syndromes mutations in the genes , , , , were detected in 55.6% of cases. In 33.3% of cases of Knobloch type 1, Cohen, Wagner syndromes the mutation is found in both copies of the gene (i.e., in both chromosomes), which leads to the development of peripheral retinal degenerations with high myopia.
CONCLUSION
The results of the conducted molecular genetic testing expand our understanding of the mutation spectrum in the genes of children with both isolated cases of ophthalmic pathology, as well as syndromic pathology.
Topics: Child; Humans; Female; Male; Child, Preschool; Adolescent; Retinal Degeneration; Mutation; Eye Diseases, Hereditary; Arthritis; Versicans
PubMed: 38450462
DOI: 10.17116/oftalma202414001119 -
Indian Journal of Ophthalmology Nov 2016We aimed to describe congenital keratoglobus with blue sclera in two siblings with overlapping Marshall/Stickler phenotype. Two sisters (ages four and six) with...
We aimed to describe congenital keratoglobus with blue sclera in two siblings with overlapping Marshall/Stickler phenotype. Two sisters (ages four and six) with bilateral high astigmatism were evaluated by slit-lamp microscopy. Corneal topography and pachymetry maps were also obtained. Slit-lamp examination revealed that both corneas were globular in shape with peripheral corneal thinning. Pachymetry maps showed diffuse corneal thinning. Two siblings had in common the features of keratoglobus, blue sclera, atypical face, hearing loss, and hypermobile joints. We tentatively diagnosed the sisters as having an overlapping Marshall-Stickler phenotype based on clinical and radiological findings. Marshall-Stickler syndrome may exist in the differential diagnosis of keratoglobus with blue sclera.
Topics: Abnormalities, Multiple; Cataract; Child; Child, Preschool; Collagen Type XI; Cornea; Corneal Topography; Craniofacial Abnormalities; Eye Diseases, Hereditary; Female; Genetic Diseases, X-Linked; Hearing Loss, Sensorineural; Humans; Osteochondrodysplasias; Phenotype; Sclera; Siblings; Visual Acuity
PubMed: 27958215
DOI: 10.4103/0301-4738.195615