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Behrad Yousefi Milani, C Summers, Irene H Maumenee; Mutation identification in the family with autosomal recessive encephalocele and retinal detachments originally described by Knobloch.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6434.
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The ocular findings in the Knobloch syndrome, in addition to retinal detachments, are characterized by incomplete macular development and congenital high myopia. Mutations in COL18 had been previously identified in this disease. Menzel et al described evidence for exclusion of the chr: 21 locus in one family with clinically indistinguishable Knobloch syndrome. No causative mutations had previously been identified in the original family with autosomal recessive encephalocele and retinal detachments described by Knobloch and Layer, 1971 and Cook and Knobloch, 1982. The search for a second causative gene for Knobloch syndrome beside COL18 had been ongoing in this as well as additional Knobloch families. The purpose of this study is to detect causative gene mutations in the large family originally described.
Peripheral blood samples for DNA extraction as well as clinical information of all living affected and potentially informative family members were obtained after informed consent was secured and the study had been approved by the Internal Review Board. DNA was extracted from one sample of the large original Knobloch family and submitted for exon sequencing of the following genes: COL18A1, ADAMTS18 and COL15.
DNA analysis showed compound heterozygosity of mutations in exon 41 of COL18A1 in the original family described by Knobloch in which meningocele, ateliotic macula and retinal detachment are described as an autosomal recessive disease.
The Knobloch syndrome is classified as heritable disorders of connective tissue and combines ocular, CNS and skeletal findings. It is a complex autosomal recessive syndrome, involving intrauterine developmental anomalies of the brain (meningoencephaloceles), the macula (ateliotic macula) and the face. Ocular complications consist of irregular astigmatism, juvenile cataracts, dislocated lenses and retinal detachments. To date, no definitive mutations beyond those in COL18 have been identified in patients with the Knobloch phenotype.
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