Gore Rachel H, Nikita Maria Eleni, Newton Paula G, Carter Rebecca G, Reyes-Bautista Jeanine, Greene Carol L
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland.
J Endocr Soc. 2020 Apr 27;4(5):bvaa027. doi: 10.1210/jendso/bvaa027. eCollection 2020 May 1.
Chromosome 6q24-related transient neonatal diabetes mellitus is characterized by intrauterine growth restriction and low birth weight, with neonatal hyperglycemia resolving by 18 months and an increased risk for type 2 diabetes in adulthood. Molecularly, it is caused by overexpression of the 6q24 imprinted chromosomal region due to a duplication, uniparental disomy, or abnormal methylation. Conventional testing for this condition analyzes methylation patterns at the 6q24 locus but does not evaluate for the presence of other surrounding chromosomal abnormalities. We report a female with a history of neonatal hyperglycemia due to a paternally inherited duplication at chromosomal location 6q24. She subsequently presented to the pediatric genetics clinic at 15 months of age with developmental delay and abnormal balance. Microarray analysis identified a larger 14 Mb chromosomal duplication from 6q24 to 6q25.2, consistent with a diagnosis of duplication 6q syndrome. This case highlights the clinical importance of pursuing further genetic evaluation in patients diagnosed with chromosome 6q24-related neonatal hyperglycemia via targeted methylation-specific multiplex ligation-dependent probe amplification analysis identifying a duplication in this region. Early identification and intervention can improve developmental outcomes for patients with larger chromosome 6q duplications.
6号染色体q24相关的短暂性新生儿糖尿病的特征为宫内生长受限和低出生体重，新生儿高血糖在18个月时缓解，成年后患2型糖尿病的风险增加。在分子层面，它是由6号染色体q24印记区域因重复、单亲二体或异常甲基化而过度表达所致。针对这种疾病的传统检测分析6号染色体q24位点的甲基化模式，但不评估其他周围染色体异常的存在情况。我们报告了一名女性，她因父系遗传的6号染色体q24位置重复而有新生儿高血糖病史。她随后在15个月大时因发育迟缓及平衡异常就诊于儿科遗传学诊所。微阵列分析确定了一个从6号染色体q24到6号染色体q25.2的更大的14 Mb染色体重复，符合6号染色体重复综合征的诊断。该病例强调了对于通过靶向甲基化特异性多重连接依赖探针扩增分析诊断为6号染色体q24相关新生儿高血糖的患者进行进一步基因评估的临床重要性，这种分析可识别该区域的重复。早期识别和干预可改善较大6号染色体q重复患者的发育结局。
