基因分析报告  Gene Analysis Report

通过对疾病相关基因的测序分析, 发现与疾病表型相关的高度可疑变异
Through sequencing analysis of disease-related genes, highly suspicious variations associated with disease phenotype were discovered

（1）基因变异信息详细解读: (1) Detailed interpretation of gene mutation information:

方法学: Methodology:

局限性: Limitations:

1. 本检测项目只针对已知的与疾病相关的基因,一些尚未明确的基因不在检测范围内。
   This detection project only covers known genes associated with diseases, and some genes that are not yet clearly defined are not within the scope of the detection.
2. 在数据分析时, 为保证数据分析的精确性, 目标区域内少部分测序质量过低的变异将被滤掉。鉴于当前医学检测技术水平的限制和受检者个体差异等原因, 本检测无法保证 100%的准确性以及 的成功率。该方法适用于所送检基因的外显子区（不包括启动子区等非编码区) 及外显子相邻 的内含子区中的点突变（检测准确率为 以上）小的缺失插入突变 (20bp 以内）(检测准确率为 以上)。 3. 对在捕获区域内的突变, 如其所在区域为高 GC 含量区, 高度重复序列区, 或者在基因组其它位置存在高度同源序列, 本方法可能存在一定的假阴性几率。部分基因存在高重复低复杂度区域或假基因,以致检测不能完全覆盖其所有外显子区，但总体覆盖度可达 以上。受捕获效率影响, 不同基因及外显子区段的覆盖度可能无法达到 。调控区及深度内含子区可能存在的致病性变异无法检测。
   During data analysis, to ensure the accuracy of the data analysis, a small portion of low-quality variants within the target region will be filtered out. Due to the limitations of current medical detection technology and individual differences of the testees, this test cannot guarantee 100% accuracy and a success rate. This method is applicable to point mutations (detection accuracy above ) and small deletions and insertions (20bp or less) (detection accuracy above ) in the exonic regions (excluding promoter regions and other non-coding regions) and the intronic regions adjacent to the exons of the genes being tested. 3. For mutations within the capture region, if the region has a high GC content, highly repetitive sequences, or there are highly similar sequences at other positions in the genome, this method may have a certain false-negative rate. Some genes have high-repeat low-complexity regions or pseudogenes, which may result in incomplete coverage of all their exonic regions, but the overall coverage can reach or more. Affected by capture efficiency, the coverage of different genes and exonic regions may not reach . Pathogenic variants in regulatory regions and deep intronic regions cannot be detected.
3. 此检测方法可以分析到小片段缺失/插入变异, 对于更大范围内的缺失/重复, 也可以分析, 但可信度会降低, 需要另一种方法验证, 可提供参考结果; NGS 无法检测出所有拷贝数变异, 如果怀疑基因存在拷贝数变异, 可以进行针对性的 aCGH、SNP array 或 MLPA 分析。此外, 未进行 NGS 测序的家系样本不提供缺失重复结果。
   This detection method can analyze small fragment deletions/insertions, and can also analyze larger deletions/duplications, but the reliability will be reduced, and another method is needed for verification, which can provide reference results; NGS cannot detect all copy number variations, if there is a suspected copy number variation in the gene, targeted aCGH, SNP array or MLPA analysis can be performed. In addition, family samples that have not undergone NGS sequencing do not provide deletion and duplication results.
4. 本方法不适于检测特殊类型变异（包括但不限于体细胞突变、深度内含子变异、动态突变、基因甲基化、假基因区域变异、复杂重组等,上述情形均为不适用于高通量检测的技术局限性范畴)。
   This method is not suitable for detecting special types of mutations (including but not limited to somatic mutations, deep intronic mutations, dynamic mutations, gene methylation, pseudogene region variations, complex rearrangements, etc., all of which are technical limitations that are not applicable to high-throughput detection).
5. 限于目前人类对疾病认识水平的局限性, 如未检出能完全解释受检者临床表型的特定基因及致病变异位点, 并不能排除受检者存在某种遗传疾病的可能性, 因为某些疾病的发病可能与其它未知基因或本方法难以检测到、或无法确定的基因变异类型有关。
   Given the current limitations in human understanding of diseases, if specific genes and pathogenic variant sites that can fully explain the clinical phenotype of the test subject are not detected, it does not rule out the possibility that the test subject may have a genetic disease, as the onset of certain diseases may be related to other unknown genes or gene variation types that are difficult to detect or cannot be determined by this method.
6. 实验室无法对医生或受检者提供的临床表型及临床怀疑疾病的真实性、准确性、全面性做出保证。由于临床表型和家族史提供不准确或不完善的样本, 存在报告位点提报不精准的风险。特定变异的遗传性是基于向实验室描述的家庭关系, 非母（源）性或非父（源）性的可能性未被排除。
   The laboratory cannot guarantee the authenticity, accuracy, and completeness of the clinical phenotypes and suspected clinical diseases provided by the doctor or the examinee. Due to inaccurate or incomplete clinical phenotypes and family histories, there is a risk of imprecise reporting of loci. The heritability of a specific variant is based on the family relationships described to the laboratory, and the possibility of non-maternal or non-paternal origin has not been excluded.
   注:
7. 如果受检者检测到了自发变异位点，该种情况下并不排除父母生殖腺镶嵌体突变的情况存在，建议遗传咨询。
   If the subject is found to have a de novo mutation site, in this case, the possibility of parental gonadal mosaicism cannot be ruled out, and genetic counseling is recommended.
8. 参考基因组版本为 GRCh37/hg19，核苷酸改变的位置信息是基于当前版本的基因组和转录本，不同基因组版本或不同转录本，这些信息可能会有所不同。
   The reference genome version is GRCh37/hg19, and the nucleotide change position information is based on the current version of the genome and transcripts. In different genome versions or different transcripts, this information may vary.
9. hom/het/hemi: hom 表示此突变位点为纯合突变, het 表示此突变位点为杂合突变, hemi 表示此突变位点为半合子突变。
   hom/het/hemi: hom indicates that the mutation site is homozygous, het indicates that the mutation site is heterozygous, and hemi indicates that the mutation site is hemizygous.
10. MAF: 正常人群频率 1000 genomes（千人基因组)、ESP6500（NHLBI Exome Sequencing Project)、EXAC (The Exome Aggregation Consortium）和 EXAC-EAS（EXAC 约 4000 东亚人数据）。
    MAF: Frequency in normal population from 1000 Genomes, ESP6500 (NHLBI Exome Sequencing Project), EXAC (The Exome Aggregation Consortium) and EXAC-EAS (EXAC approximately 4000 East Asian individuals).
11. 蛋白功能预测软件 Protein function prediction software

6. 根据美国医学遗传学与基因组学会 (ACMG）发布的变异解读指南进行致病性分析: pathogenic/致病性变异; likely pathogenic/疑似致㾄性变异; uncertain/临床意义未明变异; likely-benign/疑似良性变异; benign/良性变异。本检测只报告根据 ACMG 分级为“致病”、“疑似到病”、“临床意义未明”的变异，不报告“良性”及“疑似良性”等不具有临床意义的变异。有明确家族史的病人，如果有相关家属的基因检测绾果会更有助于定性疾病相关的突变。
   According to the variant interpretation guidelines published by the American College of Medical Genetics and Genomics (ACMG), pathogenic/pathogenic variant; likely pathogenic/likely pathogenic variant; uncertain/variant of uncertain significance; likely-benign/likely benign variant; benign/benign variant. This test only reports variants classified as "pathogenic", "likely pathogenic", or "uncertain significance" according to ACMG, and does not report "benign" or "likely benign" variants that are not clinically significant. For patients with a clear family history, genetic testing results of relevant family members will be more helpful in determining disease-associated mutations.
7. 遗传方式: AR 表示常染色体隐性遗传; AD 表示常染色体显性遗传; XR 表示 X 染色体隐性遗传; XD 表示 X 染色体显性遗传。
   Inheritance pattern: AR indicates autosomal recessive inheritance; AD indicates autosomal dominant inheritance; XR indicates X-linked recessive inheritance; XD indicates X-linked dominant inheritance.
8. 基因核苷酸变异的解释是基于目前对该基因的了解, 随着研究的深入, 这些解释也可能会发生改变。对于某些目前未知临床意义的变导或与其他疾病有关的变异未列在该报告中。
   The interpretation of the genetic nucleotide variation is based on the current understanding of the gene. As research progresses, these interpretations may change. Certain variants of unknown clinical significance or variants associated with other diseases are not included in this report.

附录 1： 家系分析结果展示 Appendix 1: Pedigree Analysis Results

注: 由于 Sanger 验证采用正向测序或反向测序, 峰图显示的碱基有可能为被检测碱基的反向互补序列, 如: c.163G>A, 峰图可显示为 G>A 或其反向互补序列 C>T。
Note: Since Sanger sequencing uses either forward or reverse sequencing, the base shown in the peak trace may be the reverse complement of the detected base, e.g., for c.163G>A, the peak trace may show G>A or its reverse complement C>T.

附录 2: 基因检测列表
Appendix 2: Gene Testing List