Dataset Information

New COL6A6 Variant Causes Autosomal Dominant Retinitis Pigmentosa in a Four-Generation Family.

ABSTRACT:

Purpose

To report that variants in the gene for a large lamina basal component protein, COL6A6 (collagen type VI alpha 6 chain, Col6α6), linked to chromosome 3p22.1 causes retinitis pigmentosa (RP) in patients with autosomal dominant transmission (adRP).

Methods

A positional-cloning approach, whole exome sequencing, and modeling were used. The proband and several affected family members have been phenotyped and followed for over 12 years.

Results

A heterozygous missense variant, c.509C>G (p. Ser170Cys) in exon 2 of COL6A6 (comprised of 36 exons and 2236 amino acids), was observed in a four- generation family and is likely to cause the adRP phenotype. It was identified in 10 affected members. All affected family members had a distinct phenotype: late-onset rod cone dystrophy, with good retained visual acuity, until their late 70s. Immunohistochemistry of human retina showed a dot-like signal at the base of the inner segments of photoreceptors and outer plexiform layer (OPL). The structural modeling of the N7 domain of Col6α6 suggests that the mutant might result in the abnormal cellular localization of collagen VI or malformation of collagen fibers resulting in the loss of its unique filament structure.

Conclusions

COL6A6 is widely expressed in human tissues and evolutionary conserved. It is thought to interact with a range of extracellular matrix components. Our findings suggest that this form of RP has long-term useful central visual acuity and a mild progression, which are important considerations for patient counseling.

SUBMITTER: Vaclavik V

PROVIDER: S-EPMC8963667 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

New COL6A6 Variant Causes Autosomal Dominant Retinitis Pigmentosa in a Four-Generation Family.

Vaclavik Veronika V Tiab Leila L Sun Young Joo YJ Mahajan Vinit B VB Moulin Alexandre A Allaman-Pillet Nathalie N Munier Francis L FL Schorderet Daniel F DF

Investigative ophthalmology & visual science 20220301 3

<h4>Purpose</h4>To report that variants in the gene for a large lamina basal component protein, COL6A6 (collagen type VI alpha 6 chain, Col6α6), linked to chromosome 3p22.1 causes retinitis pigmentosa (RP) in patients with autosomal dominant transmission (adRP).<h4>Methods</h4>A positional-cloning approach, whole exome sequencing, and modeling were used. The proband and several affected family members have been phenotyped and followed for over 12 years.<h4>Results</h4>A heterozygous missense var ...[more]

PMID: 35333290

Similar Datasets

Project description:Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, and 15-25% of RP is transmitted as an autosomal dominant (ad) trait. The objectives of this study were to establish the variant profile in a large cohort of adRP families and to elucidate the variant spectrum of each adRP gene in Chinese patients. A total of 138 probands clinically diagnosed with RP as a presumed autosomal dominant trait were recruited. All probands underwent ophthalmic examinations by specialists. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger DNA sequencing, and multiplex ligation probe amplification assay, was used to detect variants. We identified heterozygous variants of 11 adRP genes in 73 probands, hemizygous, or heterozygous variants of X-linked RP genes in six patients, compound heterozygous variants of autosomal recessive RP genes in three pseudodominant families, and one heterozygous variant of one ad cone and rod dystrophy gene in one proband. One proband was found carrying both variants in RPGR and FAM161A. The overall detection rate was 59.4% (82/138). We detected 72 distinct disease-causing variants involving 16 RP genes and one cone-rod dystrophy gene; 33 of these variants have not been reported previously. Disease-causing variants were identified in the adRP genes in 52.9% of the families, followed by 4.3% in the X-linked RP genes, and 2.2% in the autosomal recessive genes. The most frequent mutant genes were RHO, PRPF31, RP1, SNRNP200, and PRPF8, which explained up to 78.0% of the genetically diagnosed families. Most of the variants identified in adRP genes were missense, and copy number variations were common (7/20) in the PRPF31 gene. We established the profile of the mutated genes and the variant spectrum of adRP genes in a large cohort of Chinese patients, providing essential information for genetic counseling and future development of therapeutics for retinal dystrophy inherited as a dominant trait.

Dataset Information

New COL6A6 Variant Causes Autosomal Dominant Retinitis Pigmentosa in a Four-Generation Family.

Purpose

Methods

Results

Conclusions

Publications

New COL6A6 Variant Causes Autosomal Dominant Retinitis Pigmentosa in a Four-Generation Family.

Similar Datasets

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