Joost K, Tammur P, Teek R, Zilina O, Peters M, Kreile M, Lace B, Zordania R, Talvik I, Ounap K
The Centre of Excellence for Translational Medicine, Tartu University Hospital, Tartu.
Mol Syndromol. 2011 Sep;1(6):311-315. doi: 10.1159/000331323. Epub 2011 Sep 14.
Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epilepsy and biochemical changes characteristic of OTC deficiency but no identifiable point mutation in the OTC gene. Standard G-banding cytogenetic analysis, whole genome karyotyping, and X-inactivation studies were performed to determine the genetic etiology of the OTC deficiency in the patient. Results: Cytogenetic analysis and molecular karyotyping using SNP array revealed a deletion of the whole short arm of the X chromosome (Xp22.33-p11.1). Inactivation studies also revealed a completely skewed X-inactivation. Conclusion: Our patient presented with MR, epilepsy, and some evidence of reduced OTC activity, but performed genetic studies gave no explanation for this phenotype. We hope that this case report contributes to the understanding of the underlying genetic factors of the manifestation of X-linked disorders in female patients.
X染色体短臂全部或部分缺失的女性具有特纳综合征的多种特征，但智力迟钝（MR）很少发生。逃避X染色体失活的缺失基因的单倍剂量不足可能解释了MR和自闭症的发生。鸟氨酸转氨甲酰酶（OTC）缺乏症是最常见的尿素循环障碍，呈X连锁半显性遗传，OTC基因定位于Xp21。方法：我们报告了一名患有MR、癫痫且具有OTC缺乏症特征性生化变化但OTC基因未发现可识别点突变的女孩。进行了标准G显带细胞遗传学分析、全基因组核型分析和X染色体失活研究，以确定该患者OTC缺乏症的遗传病因。结果：细胞遗传学分析和使用SNP阵列的分子核型分析显示X染色体短臂全部缺失（Xp22.33-p11.1）。失活研究还显示X染色体失活完全偏向。结论：我们的患者表现出MR、癫痫以及一些OTC活性降低的证据，但进行的遗传学研究无法解释这种表型。我们希望本病例报告有助于理解女性患者X连锁疾病表现的潜在遗传因素。
