Clinical and Molecular Analysis of Enlarged Vestibular Aqueducts
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 324
- 试验地点
- 1
- 主要终点
- By using genetic linkage, identify and map possible additional mutant alleles of SLC26A4 or other genes causing nonsyndromic EVA in patients with one or no detectable mutant allele of SLC26A4
研究概览
简要总结
This study will try to identify and understand the genetic factors that lead to an inner ear malformation called "enlarged vestibular aqueducts", that can be associated with hearing loss.
Patients with sensorineural hearing loss with or without inner ear malformations and their parents and siblings may be eligible for this study. Participants and their immediate family members, may undergo some or all of the following tests and procedures:
- Medical and family history, including questions about hearing, balance and other ear-related issues, and review of medical records.
- Routine physical examination.
- Blood draw or buccal swab (brushing inside the cheek to collect cells) - Tissue is collected for DNA analysis to look for changes in genes that may be related to hearing loss.
- Hearing tests - The subject listens for tones emitted through a small earphone.
- Balance test (VEMP) to see if balance functions of the inner ear are associated with the hearing loss Electrodes will be placed behind your ear and at the base of your neck. From a reclining position, you will be asked to raise your head while clicking sounds are played into your ears. - Ultrasound tests - An inner ear malformation called EVA (enlargement of the vestibular aqueduct) indicates that a genetic disorder called Pendred syndrome may be the cause. Because thyroid abnormalities are also associated with Pendred syndrome, an ultrasound examination of the thyroid gland may be done.
- Computed tomography (CT) and magnetic resonance imaging (MRI) scans - These tests show the structure of the inner ear. For CT, the subject lies still for a short time while X-ray images are obtained. For MRI, the patient lies on a stretcher that is moved into a cylindrical machine with a strong magnetic field. The magnetic field and radio waves produce images of the inner ear. The radio waves cause loud thumping noises that can be muffled by the use of earplugs.
详细描述
Nonsyndromic hereditary hearing impairment is a genetically heterogeneous disorder that can be caused by mutations in any one of at least 60 different genes. Enlargement of the vestibular aqueduct (EVA) is a radiologic finding known to be associated with mutations in one of these genes, the Pendred syndrome gene (SLC26A4, formerly known as PDS). EVA may thus serve as a clinically useful marker to facilitate the diagnosis of hearing impairment. Recent data from our laboratory and others indicates that only a subset of individuals with EVA have SLC26A4 mutations, and therefore some EVA cases are likely to be caused by other genes, nongenetic factors, or a combination of these etiologies. Families with two or more individuals with hearing impairment and EVA will be enrolled in this study in order to identify other genetic factors that cause EVA. Siblings and parents may also be enrolled in order to define inheritance and to perform molecular genetic analyses.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Subjects must have or be a family member of a participant with known or non-syndromic SNHL associated with EVA or have evidence of other findings that suggest that EVA might be part of a novel phenotype
- •There must be at least two participating affected family members with one exception: if there is only one participating affected family member, there must be genetic test results identifying only one pathogenic mutant allele of SLC26A4
- •Adults must be able to provide informed consent
- •Minors must have a parent or guardian able to provide consent
- •Age between 0-99.
排除标准
- •Subjects with known exposure to physical or chemical teratogens in utero that could account for their inner ear malformations such as thalidomide or radiation
- •Any hearing loss that is associated with symptoms which meet the criteria of already known syndromes, such as, branchio-oto-renal (BOR) syndrome, which comprises system malformations and branchial cleft abnormalities and is caused by heterozygous mutations in the EYA1 gene.
- •Previous genetic testing identifying two pathogenic mutant alleles of SLC26A
- •Prospective study subjects who are cognitively impaired and lack consent capacity, will not be enrolled.
研究组 & 干预措施
2
Patients with nonsyndromic EVA
4
Other unaffected relatives; included if there is more than one sibship with affected family
3
unaffected siblings and parents of affected family members
1
Patients with known or suspected nonsyndromic SNHL associated with EVA
结局指标
主要结局
By using genetic linkage, identify and map possible additional mutant alleles of SLC26A4 or other genes causing nonsyndromic EVA in patients with one or no detectable mutant allele of SLC26A4
时间窗: ongoing
Identify genes other than SLC26A4 that cause EVA.
次要结局
未报告次要终点