Department of Pediatric Neurology, Duzce University Medical Faculty, 81820, Duzce, Turkey.
Department of Medical Genetics, Duzce University Medical Faculty, Duzce, Turkey.
Acta Neurol Belg. 2021 Jun;121(3):749-755. doi: 10.1007/s13760-021-01671-9. Epub 2021 Apr 10.
The purpose of this study is to reveal the effect on the clinical phenotype of variants detected at family examination of a case of combined pogo transposable element derived with zinc finger domain (POGZ) gene, tubulin folding cofactor E (TBCE) gene, and short stature homeobox (SHOX) gene variation. A Turkish non-consanguineous family consisting of five members was investigated. Whole exome sequence analysis and chromosomal microarray analysis (CMA) were performed for a 2-year-old male patient (the proband) with global developmental delay, hypotonia, dysmorphia, and hot water epilepsy. Targeted sequence and chromosomal microarray analyses were performed for each family member. A heterozygous c.3908_3911delTCTG/p.V1303fs*6 variant was detected in the POGZ gene and a heterozygous c.626 T > G(p.L209X) variant in the TBCE gene in the proband. In addition, a gain of 0.1 MB was detected in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region at CMA. The SHOX (312865) gene defined in Online Mendelian Inheritance in Man is located in this region. While the proband's father and brother had heterozygous variations only in the TBCE gene, neither TBCE nor POGZ mutations were detected in the mother or sister. A gain in Xp22.33(419224-883640) × 3 was detected in the mother at CMA. Except for short stature and Madelung deformity, no phenotypical findings were detected in the mother. Other family members were also phenotypically normal. The family screening confirmed that dysmorphic findings and global developmental delay in the proband resulted from the variation in the POGZ gene, while short stature was caused by the gain in the Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 region. In addition, the pathogenic POGZ gene variation in our patient may be a possible cause of hot water epilepsy. Heterozygous variation in the TBCE gene was clinically insignificant. Hot water epilepsy has not previously been reported in the rare patients with POGZ gene mutation. Additionally, in contrast to the previous literature, the proband exhibited no features of autism. It should also be remembered that posterior fossa abnormalities are frequently seen in these patients. We think that this case and family review involving POGZ and SHOX gene mutations will make a useful contribution to the existing literature.
本研究旨在揭示在一个同时存在 pogo 转座元件衍生锌指域（POGZ）基因、微管折叠辅助因子 E（TBCE）基因和矮小同源盒（SHOX）基因变异的家族检查中发现的变异对临床表型的影响。对一个由 5 名成员组成的土耳其非近亲家族进行了研究。对 2 岁的男性患者（先证者）进行了全外显子组测序分析和染色体微阵列分析（CMA），该患者表现为全面发育迟缓、张力减退、畸形和热水癫痫。对每个家族成员进行了靶向序列和染色体微阵列分析。在 POGZ 基因中检测到杂合 c.3908_3911delTCTG/p.V1303fs*6 变异，在 TBCE 基因中检测到杂合 c.626T > G(p.L209X) 变异。此外，在 CMA 中检测到 Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 区域的 0.1MB 增益。SHOX（312865）基因在在线孟德尔遗传数据库中定义，该基因位于该区域。虽然先证者的父亲和兄弟仅在 TBCE 基因中存在杂合变异，但在母亲或姐姐中未检测到 TBCE 或 POGZ 突变。在 CMA 中，母亲也检测到 Xp22.33(419224-883640) × 3 的增益。除了身材矮小和马德隆畸形外，母亲没有发现任何表型异常。其他家族成员的表型也正常。家族筛查证实，先证者的表型异常和全面发育迟缓是由 POGZ 基因突变引起的，而身材矮小是由 Xp22.33(602488-733497) × 3/Yp11.32(552488-683497) × 3 区域的增益引起的。此外，我们患者中致病性 POGZ 基因突变可能是热水癫痫的一个可能原因。TBCE 基因的杂合变异在临床上无意义。以前没有报道过 POGZ 基因突变的罕见患者有热水癫痫。此外，与以前的文献相比，先证者没有自闭症特征。还应记住，这些患者经常出现后颅窝异常。我们认为，涉及 POGZ 和 SHOX 基因突变的这个病例和家族综述将对现有文献做出有益贡献。
