Karantza Maria, Lee Hane, Kitsiou Sophia, Michala Lina, Spiliotis Bessie E, Dimitriou Gabriel, Kostopoulou Eirini
Mitera Children's Hospital, Athens, Greece.
, Seoul, 3billion, Republic of Korea.
Hormones (Athens). 2025 Mar;24(1):283-286. doi: 10.1007/s42000-024-00615-1. Epub 2024 Nov 25.
Variants in the GNB1 gene, which encodes for the beta-1 subunit of G proteins, have been associated with intellectual development disorder (OMIM: 616973), characterized by developmental delay, infantile hypotonia, seizures, and psychiatric problems. GNB1 variants may also cause a multisystem disorder, with symptoms such as hearing and vision impairment, gastrointestinal disorders, genitourinary abnormalities, and growth delay.
We present two pediatric patients with two novel GNB1 variants. The first patient is a 12-year old Caucasian European female with a history of neonatal hypotonia, feeding difficulties, and failure to thrive for the first 2 years of life. Subsequently, she developed grade 3 obesity, hyperphagia, and autoimmune thyroiditis. Whole Exome Sequencing (WES) revealed a novel likely pathogenic variant in the GNB1 gene (NM_002074.5:c.93_94del, p.Gln32AspfsTer46), which is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. The second patient is a 2-year old Roma female with severe failure to thrive during infancy, congenital hypothyroidism, and transient hyperoxaluria. No developmental delay was identified. Genetic testing excluded primary hyperoxaluria and WES revealed to be a novel likely pathogenic variant {NM_002074.5:c.183G > T (NP_002065.1:p.Met61Ile), which is predicted to have a damaging effect on the gene or gene product.
We present two rare pediatric cases with novel GNB1 variants which highlight the phenotypic variability associated with disrupted GNB1 expression. GNB1 may serve as a candidate gene for severe early onset obesity, hyperphagia, neurodevelopmental delay, and other metabolic and endocrine disorders.
编码G蛋白β-1亚基的GNB1基因中的变异与智力发育障碍（OMIM：616973）相关，其特征为发育迟缓、婴儿期肌张力减退、癫痫发作和精神问题。GNB1变异也可能导致一种多系统疾病，伴有听力和视力损害、胃肠道疾病、泌尿生殖系统异常和生长发育迟缓等症状。
我们报告了两名患有两种新型GNB1变异的儿科患者。第一名患者是一名12岁的欧洲白种女性，有新生儿期肌张力减退、喂养困难以及生命最初2年生长发育不良的病史。随后，她出现了3级肥胖、食欲亢进和自身免疫性甲状腺炎。全外显子测序（WES）揭示了GNB1基因中的一种新型可能致病变异（NM_002074.5:c.93_94del，p.Gln32AspfsTer46），预计该变异会通过无义介导的衰变（NMD）或蛋白质截短导致正常蛋白质功能丧失或破坏。第二名患者是一名2岁的罗姆女性，婴儿期严重生长发育不良，患有先天性甲状腺功能减退和短暂性高草酸尿症。未发现发育迟缓。基因检测排除了原发性高草酸尿症，WES显示为一种新型可能致病变异{NM_002074.5:c.183G>T（NP_002065.1:p.Met61Ile），预计该变异会对基因或基因产物产生有害影响。
我们报告了两例罕见的儿科病例，其具有新型GNB1变异，突出了与GNB1表达破坏相关的表型变异性。GNB1可能是严重早发性肥胖、食欲亢进、神经发育迟缓以及其他代谢和内分泌疾病的候选基因。
