Mutational Spectrum of Anterior Segment ophthalmic disorders

Study ID
STU 102010-032

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

Contact
Mike Molai
214-645-2014
mike.molai@utsouthwestern.edu

Principal Investigator
Venkateswara Mootha

Summary

We propose to build a repository of Dna, serum, and tissue specimens with corresponding clinical phenotypic information of 2000 pts with anterior and posterior segment disorders. This study is expected to last 72 mo. anterior segment (aS) disorders will be diagnosed based on slit lamp examination. This includes examining vision, inspection of the aS including the cornea and conjunctiva. Dilation will be performed. Posterior segment disorders will be diagnosed on funduscopic examination. in addition, tonometry will be performed in order to document intraocular pressure. at discretion of Pi, non-invasive imaging studies may be performed to document findings. age of onset of symptoms will be documented as well. Moreover, an extensive social and medical history questionnaire will be used to create a database. Smoking history and alcohol use will be documented. Medications use including HRT in women will be noted. Data will be collected and stored in a secure manner per iRB guidelines. Besides the proband, we will also recruit affected and unaffected family members (parents, siblings, and other related siblings) to this registry. approximately 40 cc (40ml / 3 tablespoons) of blood will be collected from consented individuals to create a repository consisting of both sporadic and familial patients and to the extent possible of their family members. in children weighing less than 40 lbs, 2 tps (8 ml/8cc) of blood will be collected. Recruitment will take place at the ophthalmology faculty practices at aston Center and resident/fellow clinics at PMH. Drs. Walter Beebe and Bradley Bowman at Cornea associates of Texas will identify and recruit adult-onset as well as congenital corneal disorders for the Pi's clinical research project. Dna extraction after isolation of blood lymphocytes will be performed. Separated serum will be stored in the department of ophthalmology lab facility for an indefinite period of time or until completely used in this or other research projects performed in the department of ophthalmology. additionally, the Pi may elect to share the blood and or Dna bank with other research collaborators that are researching this or other medical conditions. The de-identified genomic Dna samples will be sent to the uTSW microarray core facility for genome wide linkage analysis. Direct sequencing and mutation analysis of the genetic intervals of interest will be performed to identify potential genes of aS and PS disorders. Whole genome sequencing and global expression profiling may be performed on samples. De-identified Dna sequence data may be shared with Sequence Read archive of the national Center for Biotechnology (nCB) information maintained by the niH. De-identified gene expression data may be shared with Gene expression omnibus of the nCB information maintained by the niH. Corneal specimens from patients requiring keratoplasty for improvement in their vision and conjunctival specimens from patients requiring excisional biopsy for their care will be used for gene expression profiling to identify candidate genes and immunohistochemistry studies to confirm abnormal gene products. De-indentified skin tissue may be used to establish a cell line as a source of Dna. De- identified serum will be examined for various biomarkers that may influence the phenotype of the aS disorder. upon incidental discovery of a possible disease predisposing variant, a geneticist, Dr. Joseph Maher, will be consulted regarding the clinical significance of the variant without identifiable information being shared with him regarding the subject. if the geneticist classifies the variant as a clear-cut disease predisposing variant, the subject will be notified of the incidental finding and the physician of their choice will be notified if they had consented to the notification option in their informed consent. The patient and their physician will be given information about the appropriate genetic counseling services available to them.

Participant Eligibility

PROBAND: All of the following conditions must be met in order for the potential proband to be eligible for the study:

1. Patient of any sex and race who are 1 years of age or older. Spanish speaking patients will be encouraged to participate, Spanish forms will be available to review and execute.
2. Patient willing to review, understand, and sign written Informed Consent. Parents or legal guardians will consent on behalf of minors.
3. Written authorization for use or release of health and research study information.
4. Patient who volunteers is suffering from an anterior segment ophthalmic disorder and has member(s) of immediate and distant family who are either affected or unaffected family members.

FAMILY MEMBER: All of the following conditions must be met in order for the family member to be eligible for the study:

1. Patient of any sex and race who are 1 years of age or older. Spanish speaking patients will be encouraged to participate, Spanish forms will be available to review and execute.
2. Unaffected and affected family members of the proband will be encouraged to participate in this study.

SPORADIC CASES: Patients with anterior segment ophthalmic disorders without any family history will be encouraged to participate in this study.