Identification of POU1F1 Variants in Vietnamese Patients with Combined Pituitary Hormone Deficiency

被引:0
作者
Nguyen, Ha Thu [1 ,2 ]
Nguyen, Khanh Ngoc [1 ,2 ]
Dien, Tran Minh [3 ]
Can, Thi Bich Ngoc [2 ]
Nguyen, Thi Thanh Ngan [4 ]
Lien, Nguyen Thi Kim [4 ]
Tung, Nguyen Van [4 ]
Xuan, Nguyen Thi [4 ]
Tao, Nguyen Thien [4 ]
Nguyen, Ngoc Lan [5 ]
Tran, Van Khanh [5 ]
Mai, Tran Thi Chi [1 ]
Tran, Van Anh [1 ]
Nguyen, Huy Hoang [4 ]
Vu, Chi Dung [1 ,2 ]
机构
[1] Hanoi Med Univ, 1st Ton Tung St, Hanoi 11521, Vietnam
[2] Vietnam Natl Childrens Hosp, Ctr Endocrinol Metab Genet Genom & Mol Therapy, 18-879 Thanh, Hanoi 11512, Vietnam
[3] Vietnam Natl Childrens Hosp, 18-879 Thanh, Hanoi 11512, Vietnam
[4] Vietnam Acad Sci & Technol, Inst Genome Res, 18 Hoang Quoc Viet St, Hanoi 10072, Vietnam
[5] Hanoi Med Univ, Ctr Gene & Prot Res, 1st Ton That Tung St, Hanoi 11521, Vietnam
关键词
hypopituitarism; combined pituitary hormone deficiency; Vietnamese; c.428G>A (p.Arg143Gln); c.811C>T p.(Arg271Trp); c.557T>G p.(Leu186Arg); POU1F1; GROWTH-HORMONE; GENETIC CAUSES; PIT-1; GENE; CHILDREN; GENOME; MUTATIONS; HEIGHT; DNA;
D O I
10.3390/ijms26062406
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency.
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页数:14
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