An Early Diagnostic Clue for COL18A1- and LAMA1-Associated Diseases: High Myopia With Alopecia Areata in the Cranial Midline.
An Early Diagnostic Clue for COL18A1- and LAMA1-Associated Diseases: High Myopia With Alopecia Areata in the Cranial Midline.
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COL18A1 和 LAMA1 相关疾病的早期诊断线索：高度近视伴颅骨中线斑秃
DOI：
10.3389/fcell.2021.644947
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Wang P;Jia X;Xiao X;Li S;Long Y;Liu M;Li Y;Li J;Xu Y;Zhang Q
在COL18A1突变引起的Knobloch综合征患者中观察到高度近视伴枕区斑秃。本研究探讨了颅中线斑秃患者高度近视的其他可能的遗传原因。研究对象为6例早发性高度近视伴头中线斑秃患者。对先证者的DNA进行靶向高通量测序，检测潜在的致病变异。对可用的家庭成员进行共分离分析。使用mini基因分析和RNA测序来验证可能的剪接变化和严重缺失的异常。进行眼科和神经影像学检查。在所有6名患者中检测到8种新的和1种已知的功能丧失突变，包括通过RNA测序检测到的总缺失。3例枕区头皮松弛患者的4个COL18A1突变体3例顶叶区头皮松弛患者出现5个LAMA1突变。进一步评估表明COL18A1突变患者为Knobloch综合征，LAMA1突变患者为Poretti-Boltshauser综合征。我们的研究发现，早发性高度近视合并中线斑秃不仅可能由COL18A1基因突变引起，也可能由LAMA1基因突变引起。据我们所知，我们是第一个在LAMA1突变患者中观察到头皮缺陷的人。高度近视伴颅中线斑秃可作为眼科医生考虑两种罕见病的早期诊断线索。
High myopia with alopecia areata in the occipital region has been observed in patients with Knobloch syndrome caused by COL18A1 mutations. This study investigated other possible genetic causes of high myopia in patients with alopecia areata in the cranial midline. Six patients with early onset high myopia and alopecia areata in the cranial midline were recruited. Targeted high-throughput sequencing was performed on the proband’s DNA to detect potential pathogenic variants. Cosegregation analysis was performed for available family members. Minigene assay and RNA Sequencing were used to validate the abnormality of possible splicing change and gross deletion. Ophthalmological and neuroimaging examinations were performed. Eight novel and one known loss-of-function mutants were detected in all six patients, including a gross deletion detected by RNA sequencing. Four COL18A1 mutants in three patients with scalp leisure in the occipital region; and five LAMA1 mutations in three patients with scalp leisure in the parietal region. Further assessments indicated that patients with COL18A1 mutations had Knobloch syndrome, and the patients with LAMA1 mutations had Poretti–Boltshauser syndrome. Our study found that early onset high myopia with midline alopecia areata could be caused not only by mutations of the COL18A1 gene but also by mutations in the LAMA1 gene. To our knowledge, we are the first to observe scalp defects in patients with LAMA1 mutations. High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases.
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影响因子：
4.4
作者：
Li, Jiali;Gao, Bei;Zhang, Qingjiong
通讯作者：
Zhang, Qingjiong
影响因子：
9.8
作者：
Schuurs-Hoeijmakers, Janneke H. M.;Oh, Edwin C.;Brunner, Han G.
通讯作者：
Brunner, Han G.
影响因子：
9.8
作者：
Ackerman, Christine;Locke, Adam E.;Maslen, Cheryl L.
通讯作者：
Maslen, Cheryl L.
影响因子：
9.8
作者：
Aldinger, Kimberly A.;Mosca, Stephen J.;Doherty, Dan
通讯作者：
Doherty, Dan
影响因子：
1.2
作者：
Balikova, Irina;Sanak, Nuri Serdal;Cordonnier, Monique
通讯作者：
Cordonnier, Monique