Abstract：
OBJECTIVE: To explore the genetic background and clinical phenotypes of multiple idiopathic cervical root resorption (MICRR) in a Chinese family.
METHODS: The proband and his three family members were clinically examined and had radiographs taken with a radiovisiography (RVG) system and CBCT to define the diagnosis of MICRR. Genomic DNA (gDNA) was extracted from peripheral blood samples of the patient, his father, mother and younger sister for whole exome sequencing (WES). The pathogenicity of rare variants with minor allele frequency (MAF) less than 0.005 were analysed following possible inheritance patterns, predicted results from 12 software programs, the American College of Medical Genetics (ACMG) 2015 criteria, and information from ClinVar, OMIM and HGMD databases as well as gene function.
RESULTS: The proband presented the typical MICRR phenotypes such as thin cervical pulp wall and apple core-like lesions in radiographs. Following the recessive inheritance pattern, WES analysis identified SHROOM2, SYTL5, MAGED1 and FLNA with a higher chance of causing MICRR. Four genes with compound heterozygous variants and another 27 genes with de novo variants either in autosomal-dominant or autosomal-recessive pattern were also found to have the potential pathogenicity.
CONCLUSIONS: A total of 35 novel potential pathogenic genes were found to be associated with MICRR from a Chinese family through WES. The new genetic background of MICRR may be helpful for clinical and molecular diagnosis.
METHODS: The proband and his three family members were clinically examined and had radiographs taken with a radiovisiography (RVG) system and CBCT to define the diagnosis of MICRR. Genomic DNA (gDNA) was extracted from peripheral blood samples of the patient, his father, mother and younger sister for whole exome sequencing (WES). The pathogenicity of rare variants with minor allele frequency (MAF) less than 0.005 were analysed following possible inheritance patterns, predicted results from 12 software programs, the American College of Medical Genetics (ACMG) 2015 criteria, and information from ClinVar, OMIM and HGMD databases as well as gene function.
RESULTS: The proband presented the typical MICRR phenotypes such as thin cervical pulp wall and apple core-like lesions in radiographs. Following the recessive inheritance pattern, WES analysis identified SHROOM2, SYTL5, MAGED1 and FLNA with a higher chance of causing MICRR. Four genes with compound heterozygous variants and another 27 genes with de novo variants either in autosomal-dominant or autosomal-recessive pattern were also found to have the potential pathogenicity.
CONCLUSIONS: A total of 35 novel potential pathogenic genes were found to be associated with MICRR from a Chinese family through WES. The new genetic background of MICRR may be helpful for clinical and molecular diagnosis.
摘要：
目的：探讨中国家族中多个特发性宫颈根吸收（MICRR）的遗传背景和临床表型。
方法：先证者及其三个家庭成员进行了临床检查，并通过放射造影（RVG）系统和CBCT进行了X线片检查，以确定MICRR的诊断。从患者外周血样本中提取基因组DNA(gDNA),他的父亲,母亲和妹妹进行全外显子组测序(WES)。根据可能的遗传模式分析了次要等位基因频率（MAF）小于0.005的罕见变异的致病性。12个软件程序的预测结果，美国医学遗传学学院(ACMG)2015年标准，还有ClinVar的信息,OMIM和HGMD数据库以及基因功能。
结果：先证者表现出典型的MICRR表型，例如宫颈浆壁薄和苹果核样病变。按照隐性遗传模式，WES分析确定SHROOM2，SYTL5，MAGED1和FLNA具有较高的引起MICRR的机会。还发现四个具有复合杂合变体的基因和另外27个具有常染色体显性或常染色体隐性模式的从头变体的基因具有潜在的致病性。
结论：通过WES从一个中国家族发现了35个新的潜在致病基因与MICRR相关。MICRR的新遗传背景可能有助于临床和分子诊断。
方法：先证者及其三个家庭成员进行了临床检查，并通过放射造影（RVG）系统和CBCT进行了X线片检查，以确定MICRR的诊断。从患者外周血样本中提取基因组DNA(gDNA),他的父亲,母亲和妹妹进行全外显子组测序(WES)。根据可能的遗传模式分析了次要等位基因频率（MAF）小于0.005的罕见变异的致病性。12个软件程序的预测结果，美国医学遗传学学院(ACMG)2015年标准，还有ClinVar的信息,OMIM和HGMD数据库以及基因功能。
结果：先证者表现出典型的MICRR表型，例如宫颈浆壁薄和苹果核样病变。按照隐性遗传模式，WES分析确定SHROOM2，SYTL5，MAGED1和FLNA具有较高的引起MICRR的机会。还发现四个具有复合杂合变体的基因和另外27个具有常染色体显性或常染色体隐性模式的从头变体的基因具有潜在的致病性。
结论：通过WES从一个中国家族发现了35个新的潜在致病基因与MICRR相关。MICRR的新遗传背景可能有助于临床和分子诊断。
