The Hospital for Sick Children, Department of Paediatric Laboratory Medicine, Toronto, Ontario, Canada.
Am J Med Genet A. 2012 Nov;158A(11):2946-52. doi: 10.1002/ajmg.a.35619. Epub 2012 Sep 17.
Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by mutations involving WTX (FAM123B), a tumor suppressor protein with dual functions. OSCS typically affects females whereas males generally have fetal or neonatal lethality. Surviving affected males have characteristic facial dysmorphisms, skeletal features such as macrocephaly and short stature, neurodevelopmental disabilities and a high prevalence of neuromuscular anomalies. On imaging, hemizygous males display marked cranial and peripheral skeletal sclerosis without the metaphyseal striations that are seen in women with OSCS. Observations of striation in males may be indicative of a somatic mosaic mutation in WTX. To date only two cases of surviving males haves been confirmed with mosaic point mutations in WTX. We report on the first case of a male with a mosaic deletion of the entire WTX gene. We show that a mosaic deletion in a hemizygous male patient can cause a mild phenotype of OSCS, including facial and skull base bone striations, nasal stenosis, conductive hearing loss, global developmental delay, and mild facial dysmorphology without short stature or macrocephaly.
颅骨硬化性条纹性骨病（OSCS）是一种 X 连锁疾病，由涉及 WTX（FAM123B）的突变引起，WTX 是一种具有双重功能的肿瘤抑制蛋白。OSCS 通常影响女性，而男性通常在胎儿或新生儿期死亡。存活的受影响男性具有特征性的面部畸形、骨骼特征，如大头畸形和身材矮小、神经发育障碍以及神经肌肉异常的高发率。在影像学上，杂合子男性表现出明显的颅面和外周骨骼硬化，而女性 OSCS 则无干骺端条纹。男性条纹的观察可能表明 WTX 存在体细胞镶嵌突变。迄今为止，仅确认了两名存活男性存在 WTX 点突变镶嵌。我们报告了首例 WTX 全基因缺失的男性病例。我们表明，杂合子男性患者的镶嵌缺失可导致 OSCS 的轻度表型，包括面部和颅底骨条纹、鼻狭窄、传导性听力损失、全面发育迟缓以及轻度面部畸形，而无身材矮小或大头畸形。
