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首页> 外文期刊>Molecular syndromology >The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity
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The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity

机译：无父母亲的患者纯合子单次连续连续伸展的诊断效用

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We present data from our clinical department's experience with chromosomal microarray analysis (CMA) regarding the diagnostic utility of 1 or 2 long contiguous stretches of homozygosity (LCSHs) in an outbred population. The study group consisted of 2,110 consecutive patients from 2011 to 2014 for whom CMA was performed. The minimum cut-off size for defining a homozygous stretch was 5 Mb. To focus on cases with no parental consanguinity, we further studied only patients in whom the total length of homozygous stretches did not exceed 28 Mb or 1% of the autosomal genome length. We identified 6 chromosomal regions where homozygous stretches appeared in at least 3 patients and excluded these from further analysis. In 2 out of 120 patients with an isolated finding of 1 or 2 non-recurrent LCSHs, a plausible candidate gene associated with their phenotype was identified within the homozygous stretch. In both of these cases, a pathogenic mutation was detected, leading to diagnoses of pyruvate kinase deficiency and Marinesco-Sjögren syndrome. To clarify whether previously found homozygous stretches could be important for the interpretation of genome-wide sequencing data, we report 7 cases in which homozygous stretches not encompassing a clinically associated gene were first found on CMA, followed by the diagnostic whole-exome sequencing. The diagnostic utility of single LCSHs, unlikely to be caused by uniparental disomy, is discussed in detail.
机译：我们提供来自临床部门在染色体微阵列分析（CMA）方面的经验数据，这些数据涉及近交人群中1或2个连续连续纯合子（LCSH）的诊断实用性。该研究小组包括2011年至2014年连续进行CMA的2,110例患者。定义纯合延伸的最小截止大小为5 Mb。为了关注没有亲属血缘关系的病例，我们进一步研究了纯合延伸的总长度不超过28 Mb或常染色体基因组长度的1％的患者。我们确定了至少3名患者出现纯合伸展的6个染色体区域，并将其排除在进一步分析之外。在120例患者中，有2例单独发现1或2个非复发性LCSH，在纯合子链段中发现了与其表型相关的合理候选基因。在这两种情况下，均检测到致病性突变，从而诊断出丙酮酸激酶缺乏症和Marinesco-Sjögren综合征。为了澄清以前发现的纯合片段对解释全基因组测序数据是否重要，我们报道了7例首次在CMA上发现不包含临床相关基因的纯合片段，然后进行诊断的全外显子测序。详细讨论了不可能由单亲二体性引起的单个LCSH的诊断实用性。

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