A pedigree study of laryngo-onycho-cutaneous syndrome with a novel mutation on LAMA3 gene
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摘要: 目的 报道1例喉甲皮肤综合征，检测其基因突变，探讨可能的分子生物学致病原因。方法 采集先证者及其父母的外周血，提取DNA，高通量测序方法进行基因检测，对先证者及其家属进行突变位点的Sanger测序验证分析。结果 先证者基因检测发现LAMA3基因c.171+1G>A位点纯合突变，为剪接突变，是新发突变位点。先证者父母表型正常，基因检测出该位点杂合突变。结论 LAMA3基因c.171+1G>A纯合突变是先证者的可疑致病突变，该研究扩充了LAMA3基因的突变谱；喉甲皮肤综合征的临床表型表达具有高度可变性，多学科联合诊疗可有效避免漏诊和误诊。Abstract: Objective To detect genetic mutations in a case of laryngo-onycho-cutaneous syndrome, and to explore the possible molecular biological pathogenic causes.Methods With informed consent, the family clinical data of the child with laryngo-onycho-cutaneous syndrome were collected, peripheral blood of the protester and his parents was collected and DNA was extracted, and gene detection was performed by high-throughput sequencing method. Sanger sequencing was used to verify and analyze the mutation sites of the probs and their families.Results Genetic testing of the proband revealed homozygous mutation of LAMA3 gene c.171+1G>A site, which is splicing mutation. There was no report in the literature, which was a new mutation site. The parents of the proband had normal phenotype and heterozygous mutation at this locus was detected.Conclusion Homozygous mutation of LAMA3 c.171+1G>A is the likely pathogenic of the proband, and this study expands the mutant spectrum of LAMA3. The clinical phenotype of laryngo-onycho-cutaneous syndrome is highly variable, and the multidisciplinary diagnosis and treatment can effectively avoid missed diagnosis and misdiagnosis.
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Key words:
- laryngo-onycho-cutaneous syndrome /
- LAMA3 gene /
- DNA mutational analysis
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表 1 先证者LAMA3基因c.171+1G>A纯合突变
基因 染色体位置 转录本外显子 核苷酸氨基酸 纯合/杂合 正常人频率 REVEL预测 致病性分析 疾病/表型 遗传方式 变异来源 LAMA3 chr18-21453180 NM_001127718；exonl c.171+1G>A(splicing) hom 未知 未知 疑似致病性变异 ①LOCs；②Herlitz型交界型大疱性表皮松解症；③非Herlitz型交界型大疱性表皮松解症 ①常染色体隐性遗传；②常染色体隐性遗传；③常染色体隐性遗传 父母 
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