Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
Chinese Research Center for Behavior Medicine in Growth and Development, Jining, China.
Mol Genet Genomic Med. 2020 Sep;8(9):e1385. doi: 10.1002/mgg3.1385. Epub 2020 Jun 29.
SHORT syndrome is a rare inherited multisystem disease that includes characteristic facial features, growth retardation, and metabolic anomalies and is related to heterozygous mutations in the PIK3R1 gene. However, it is difficult to ascertain the relationship between the phenotype and the genotype quickly and efficiently.
We report two Chinese girls with SHORT syndrome who presented with growth retardation, dysmorphic features, insulin resistance, and diabetes. Comprehensive medical evaluations were collected, including anthropometric measurements, laboratory measurements, and imaging examinations. Whole exome and Sanger sequencing was performed to detect and confirm the underlying genetic mutations in these patients. We prescribed metformin for the patients.
The patients both presented diabetes, insulin resistance, short stature, lipodystrophy, and characteristic facial dysmorphic features. A heterozygous mutation was detected in the PIK3R1 gene (c.1615_1617del) of Patient 1. The analysis of patient 2 revealed another PIK3R1 mutation (c.1945C>T). After family validation, neither their parents nor their brothers had similar clinical presentations or carried the same mutation.
We identified two de novo heterozygous mutations in PIK3R1 as the cause of SHORT syndrome in two Chinese girls. Additionally, in terms of diabetes control, metformin works well in the early treatment stage.
SHORT 综合征是一种罕见的遗传性多系统疾病，包括特征性面部特征、生长迟缓以及代谢异常，与 PIK3R1 基因的杂合突变有关。然而，快速有效地确定表型与基因型之间的关系是困难的。
我们报告了两名患有 SHORT 综合征的中国女孩，她们表现为生长迟缓、畸形特征、胰岛素抵抗和糖尿病。收集了全面的医学评估，包括人体测量、实验室测量和影像学检查。对这些患者进行了全外显子组和 Sanger 测序，以检测和确认潜在的遗传突变。我们为患者开了二甲双胍。
患者均表现为糖尿病、胰岛素抵抗、身材矮小、脂肪营养不良和特征性面部畸形。患者 1 的 PIK3R1 基因（c.1615_1617del）检测到杂合突变。对患者 2 的分析显示另一个 PIK3R1 突变（c.1945C>T）。经家系验证，其父母和兄弟均无类似临床表现或携带相同突变。
我们在两名中国女孩中发现了 PIK3R1 的两个新生杂合突变，导致 SHORT 综合征。此外，在糖尿病控制方面，二甲双胍在早期治疗阶段效果良好。
