Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2
Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2
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DOI：
10.1002/ajmg.a.38655
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发表时间：
2018-05-01
影响因子：
2
通讯作者：
Abdel-Salam, Ghada M. H.
中科院分区：
文献类型：
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作者：
El-Ruby, Mona;Fayez, Alaa El-Din;Abdel-Salam, Ghada M. H.
我们报告了两名患有额鼻发育不良2型(FND-2)的无关男孩，他们都有一个相同的新的纯合子ALX4突变c.291delG(p.Q98Sfs*83)。两位患者都有较大的颅骨缺损，但其中一位有双侧顶骨脑膜膨出样囊肿，与骨缺损合在一起，且大小随年龄增长而增大。头皮脱发、脱发和鼻翼裂伤也在这两个病例中被检测到。此外，还注意到隐匿的性腺，其中一个是单侧的，另一个是双侧的。神经影像显示小的发育不良的枕叶伴有脑回障碍和中线蛛网膜下腔囊肿。在1例患者中，观察到另外的发育不良的胼胝体和小脑虫。一名患者的父母发现有顶孔。我们的发现强调了ALX4的剂量效应，并强调了产前遗传咨询的挑战。此外，还讨论了ALX4在枕叶和后颅窝发育中的间接作用。
We report two unrelated boys with frontonasal dysplasias type-2 (FND-2) who shared an identical novel homozygous ALX4 mutation c.291delG (p.Q98Sfs*83). Both patients presented with a large skull defect but one had bilateral parietal meningocele-like cysts that lie along with the bony defect and increased in size with age. Scalp alopecia, hypertelorism, and clefted alae nasi were also detected in both of them. Furthermore, impalpable gonads were noted, being unilateral in one and bilateral in the other. Neuroimaging showed small dysplastic occipital lobes with dysgyria and midline subarachnoid cyst. Additional dysplastic corpus callosum and small cerebellar vermis were observed in one patient. Parietal foramina were noted in the parents of one patient. Our findings highlight the dosage effect of ALX4 and underscore the challenges of prenatal genetic counseling. Further, the indirect role of ALX4 in the development of the occipital lobe and posterior fossa is discussed.