基因检测

经验丰富的医生可以通过体格检查诊断出前列腺增生症患者，准确率很高，但要确定诊断结果，还需要进行基因检测。检测还可以确定患者是否患有 1 型或 2 型. .要参加研究和临床试验，以及将来接受针对前列腺增生症遗传病因的治疗，也需要进行基因检测。.

如果您

• 有前列腺增生症症状，希望确认类型。.
• 有前列腺增生症家族史但无症状。.
• 计划要孩子，希望了解风险。.
• 希望有资格参与临床试验。.
• 希望获得未来的治疗.

遗传咨询师可以帮助您决定测试是否适合您。.

被检测者需要提供 DNA 样本，通常是通过抽血采集。DNA 也可以从皮肤、唾液（含有口腔细胞）等处获取。但对于基因检测来说，血液样本是标准样本。.

FSHD Type 1 results from the shortening (“contraction”) of a stretch of DNA near the tip of chromosome 4. The “FSHD region” on chromosome 4 consists of many units called D4Z4, which are repeated like beads on a string. Having more than 10 beads is protective, but if an individual has fewer than 10, then he/she is at risk for FSHD. The reduced number of D4Z4 units results in an increased chance for the expression of a gene called DUX4, which is normally locked up and silent in adult cells. This shortened, or “contracted”, chromosome must be combined with a “permissive” 4qA polyadenylation site in for the DUX4 gene to be expressed in a stable form. When this happens, it leads to damage and death of muscle cells.

多年来，FSHD1 的标准检测方法一直采用一种名为 南方印迹, 其中包括提取病人的 DNA，将长的 DNA 链切成小块，然后按大小将小块分开。然后将DNA片段转移到膜上并进行探针检测，以粗略估计D4Z4重复序列的数量。.

最近，一种名为 全基因组光学绘图 通过这种方法，我们可以在超细管中像拉线一样拉出很长的 DNA 链，然后用荧光标签探测，在显微镜下直接计算 D4Z4 单元的数量。Southern 印迹法耗时长，而且只能估计 D4Z4 单位的数量，而全基因组光学绘图法则更快更精确。.

基因检测报告会给出两个数字，分别代表等位基因 1 和等位基因 2（每个人都有两个 4 号染色体拷贝）。根据检测方法的不同，您可能会收到一份提供 D4Z4 重复序列数或 D4Z4 区域估计大小（以千碱基为单位）的报告。.

FSHD2的基因检测包括对18号染色体上名为SMCHD1的基因进行测序，以检测出可能导致FSHD2的所有变体或突变体。此外，还要检测 4 号染色体是否存在 “允许 ”的 4qA 等位基因。.

该决策树（右上图）描述了如何进行 FSHD 基因检测。. (参考文献：Tawil 等，《神经病学》，2015 年）

遗传咨询师是接受过遗传学和心理咨询专业培训的医疗保健专业人员。遗传咨询师可以帮助您

• 了解前列腺增生症和您的检测结果。.
• 了解家庭风险。.
• 就检测和计划生育做出知情决定。.
• 找到与前列腺增生症共存的应对策略。.

一个误解是，遗传咨询只适用于决定要不要孩子和使用生殖检测方案的人。事实上，处于各种不同情况和生命阶段的人都可能从遗传咨询中受益。.

请咨询您的神经肌肉专科医生或搜索 www.findageneticcounselor.com. .还有一些 “远程医疗公司，如 Genome Medical，雇用有执照的遗传咨询师，通过电话或视频提供咨询。.

Within the U.S.

比奥纳诺实验室（美国）

网站： bionanolaboratories.com

• FSHD1 检测和遗传咨询

Revvity Omics（美国）

网站： https://www.revvity.com/category/clinical-genomic-services

联系表格： https://www.revvity.com/contact-us

• FSHD 2 检测

爱荷华大学诊断实验室（美国）

客户服务电话：(866) 844-2522

玛丽-苏-奥蒂斯，UI 诊断实验室经理。.
电子邮件： marysue-otis@uiowa.edu 电话：(319) 356-3339 传真：(319) 384-7213。.

Steven A. Moore，医学博士，病理学教授。.
电子邮件： steven-moore@uiowa.edu 电话：319-335-8215：319-335-8215.

提供测试：

• FSHD1 全基因组光学图谱检测；FSHD2 SMCHD1 测序；甲基化检测（FSHD1 和 FSHD2）。详情和申请表请点击此处： 异常等位基因的检测及解释（FSHD1 和 FSHD2）. .阅读 新闻稿 about Bionano’s Saphyr optical mapping technology used for this test.
• 产前诊断和 4qA/4qB 等位基因检测。产前样本应在 6 个 T-25 烧瓶中培养至 100% 汇合，且不得冷冻。.
• 海外客户 可使用以下方式通过联邦快递连夜将标本寄往 UIDL 国际 MD 申请表. 实验室要求在检测前付款。可使用信用卡。.

Greenwood Genetic Center (U.S.)

网站： https://ggc.org/

• Optical Genome Mapping (OGM) – FSHD1 is used to detect genetic differences associated with facioscapulohumeral muscular dystrophy (FSHD) type 1. Learn more 这里.
• Greenwood Genetic Center offers a 40% self-pay discount.

Praxis Genomics（美国）

Optical Genome Mapping (OGM) can determine whether the patient has FSHD1 and whole genome sequencing using Illumina technology (ISR) can diagnose FSHD2. Praxis Genomics offers testing for FSHD1 and FSHD2 individually, as well as in combination. View their 测试清单.

Outside of the U.S.

Your doctor can order genetic testing. Let your Primary Care Provider or General Practitioner know that you are interested in getting tested for FSHD, and they should refer you to a Neurologist or Neuromuscular Specialist who can complete the test for you.

如需全球基因检测实验室的完整列表，请访问：

• 基因检测实验室在线国际目录 - 搜索 FSHD 并单击 “测试 ”选项卡。.
• NCBI 基因检测注册中心 - 点击 “测试 ”链接

If you have previously been tested, you should be able to contact the lab and ask for a copy to be sent. They will require a signed consent form so that they can release the test report to you. 

You should ask to be tested for FSHD2. If you are negative for both FSHD1 and FSHD2, you may wish to be screened by Revvity Omics comprehensive neuromuscular disease panel or for other muscular disorders through 英维泰综合神经肌肉疾病小组. 

About 2 percent of FSHD cases are of unknown genetic origin. If your tests rule out any known genetic muscle diseases, please contact us . We can connect you with researchers who are interested in collecting DNA samples from you to try to identify novel genes that cause FSHD and other muscle diseases. 

Southern 印迹检测曾是黄金标准。2020 年前接受过前列腺增生症检测的人可能都接受过这种检测。.

FSHD1 检测报告提供了包含 D4Z4 重复区域的 DNA 片段的估计大小（以千碱基为单位）。报告可能如下所示

了解检测结果：个人的两个等位基因（4号染色体各一个）都要进行前列腺肥大检测。首先，用一种名为 EcoRI 的酶切割每条 DNA 链，然后用另一种名为 BlnI 的酶进一步切割 DNA 链，检查 DNA 链的排列是否异常。 .

结果显示未受影响的 4 号染色体（等位基因 1）和受影响的 4 号染色体（等位基因 2）。D4Z4 重复数是根据 EcoRI 片段大小按此公式计算得出的：

(片段大小减 5）除以 3.3 = 重复次数

在等位基因 1 上，该片段的长度大于 40 千碱基 (kb)，因此，根据上述公式，估计重复次数为 10.6（因为 (40 - 5)/3.3 或 35/3.3 等于 10.6），因此属于非前列腺增生症范围。等位基因 2 有 4 个重复序列（因为 (18 - 5)/3.3 或 13/3.3 等于 4），这表明存在前列腺增生症。.

缺失的大小似乎与前列腺增生症的严重程度和发病年龄有关。大的缺失（导致非常小的片段）似乎与更早发病和更严重的症状有关。此外，大缺失更可能是散发性的，而不是遗传性的。小片段缺失往往与发病较晚和症状较轻有关。但研究也显示了这一趋势的例外情况。这意味着还有其他因素（可能是遗传或环境因素）会影响个体症状的严重程度。.

大约 98% 的前列腺肥大症患者可以通过 DNA 检测准确确诊。在某些前列腺增生症家族中，有些人虽然存在缺失，但并没有表现出明显的前列腺增生症症状。当D4Z4单位的数量接近正常时，这种情况更容易发生。耐人寻味的是，在普通人群中，有1%-2%的非前列腺增生症患者在第4号染色体的同一区域出现相同的缺失（D4Z4单位缺失）。这一发现在意大利人群中的意义尚不清楚。.

It depends on the study. Contact the study coordinator to ask if testing is required.

For more information about current trials and studies, visit our webpage.

Your doctor or genetic counselor can help appeal a denial. You can use our 信函模板 to help with your appeal. If not covered, you may consider paying out-of-pocket. Some labs offer financial assistance programs, like Greenwood Genetic Center.

Health insurance is protected under the Genetic Information Nondiscrimination Act (GINA), but life and disability insurance are not. Some people choose to get insurance 之前 genetic testing. Individuals with FSHD have successfully appealed the denial of life insurance by arguing that FSHD does not shorten life expectancy significantly. 

The Affordable Care Act and the Americans with Disabilities Act also provide protections for people affected by or at risk for genetic conditions. Some states have laws that prohibit genetic discrimination for these other types of insurance. More information about genetic discrimination and related laws can be found 这里. 

FSHD（Facioscapulohumeral Muscular Dystrophy）是一种使肌肉变弱的遗传病。有两种类型：

• FSHD 1 型（FSHD1） - 最常见的类型，由第 4 号染色体上缺失的遗传物质引起。.
• FSHD 2 型（FSHD2） - 由 18 号染色体上的 SMCHD1 基因变化引起。.

这两种类型都会导致一种名为 DUX4, 会伤害肌肉细胞。这两种前列腺增生症的症状也相同。.

Learn more here.

No. About 80% of people with the FSHD genotype will develop symptoms, while 20% who test positive are asymptomatic (do not have symptoms). Symptoms may appear later in life or be so mild they go unnoticed. 

Sporadic or “de novo” (meaning “new”) FSHD means a single individual in a family has FSHD, but no one else in the family has the condition. To prove a case is sporadic, both parents would need to be genetically confirmed to not have the D4Z4 deletion. Because individuals can have the D4Z4 deletion and not show symptoms, if both parents have not been tested, a seemingly sporadic case could in fact be inherited. 

It depends on the study. Contact the study coordinator to ask if testing is required.

For more information about current trials and studies, visit our webpage.

严重程度和发病取决于遗传和非遗传因素。研究人员仍在研究影响病情发展的因素。. 

• FSHD1： A child of an affected parent has a 50% 机会 of inheriting it. 

• FSHD2： The risk depends on both parents’ genetics but is at least 25-50%. 

Individuals with FSHD Type 1 have a 50 percent chance of passing FSHD to each child. With Type 2, two genes on separate chromosomes (SMCHD1 on chromosome 18 and the polyA haplotype on chromosome 4) must both be inherited to transmit FSHD, so the risk is smaller, 25-50 percent depending on the parents’ genetic makeup. 

遗传咨询可以根据家族病史提供更清晰的信息。. 

Up to 20 percent of apparently sporadic cases of FSHD arise due to 镶嵌 for the FSHD deletion in one parent. This means that one parent has a mixture of cells: some with the deletion and some without the deletion. If the deletion occurs in the egg or sperm cells of the parent, but other cells in the body do not have the deletion, a genetic test (e.g. from blood or skin) of the parent would show no FSHD, and yet the parent can pass FSHD on to multiple offspring. Therefore, there is a risk of having another child with FSHD, even if there is no detectable deletion in either parent. 

FSHD does 不 skip generations, but some individuals may never develop symptoms while their children do, making it seem like the condition skipped a generation. 

• 植入前基因检测（PGT）： This is a procedure in which in vitro fertilization is used to produce multiple embryos in a test tube. At the eight-cell stage, a single cell is removed and tested. Only embryos that test negative for FSHD are implanted. An important aspect to know about PGD is that because only one strand of DNA is available for testing, the number of D4Z4 units cannot be directly determined. Instead, DNA from the affected parent and another affected relative is analyzed for “markers” located close to the D4Z4 region. The embryonic DNA is then analyzed for the presence of those markers. Because parts of chromosomes can get rearranged, sometimes the marker and the D4Z4 region are not inherited together, so this method is not 100 percent accurate. Therefore, if parents opt for PGD, a prenatal test is usually recommended as a follow-up to be sure the deletion was not passed on. 

• 产前检测： Tests during pregnancy (CVS or amniocentesis) to check if the baby has FSHD. 

• 捐献卵子/精子： Ensures the child does not inherit FSHD. 

• 领养或代孕： Alternative ways to build a family. 

Women with FSHD must be aware that pregnancy can cause increased muscle weakness, which usually does not go back to baseline. For this reason, some women choose to use a gestational carrier (surrogate). In this option, an embryo or embryos created by IVF (either using the woman’s own eggs or donor eggs) are transferred to the womb of another woman who carries the pregnancy to term. Women with FSHD should speak to their neuromuscular specialist prior to becoming pregnant. 

Individuals and couples consider many different factors when deciding how to build their family.  Talk to a genetic counselor to learn more about all of these options, including the advantages, disadvantages, limitations, and risks so you can make the choice that’s right for you. 

可以。利用与上述 DNA 检测相同的技术，可以进行产前检测。有兴趣进行前列腺增生症产前检测的人应咨询医生和基因检测实验室。. 

In prenatal diagnosis, fetal cells are obtained primarily by one of two procedures. The earliest procedure is called chorionic villus sampling (CVS). This procedure is performed at about the tenth to twelfth week of pregnancy. The alternative procedure is called amniocentesis. This procedure is performed at about the fifteenth to sixteenth week of pregnancy. Individuals at risk of having a child with FSHD should see a geneticist for counseling as early as possible in the pregnancy or even before becoming pregnant, since it is necessary for their DNA to be tested in order to obtain accurate results. Prenatal diagnosis must be arranged many weeks in advance, through a genetics clinic. Prenatal tests have risks associated with them, and therefore it is important to obtain genetic counseling and consider all the information about prenatal testing carefully before deciding to proceed. In general, molecular diagnostic laboratories make a special effort to process prenatal DNA samples as rapidly as possible.