Novel Insights: A Novel PHIP Variant in a Family with Severe Early-Onset Obesity

被引:1
作者
Loid, Petra [1 ,2 ,3 ]
Vuorela, Nina [4 ,5 ]
Aaltonen, Kirsimari [6 ,7 ]
Kuittinen, Juha [8 ]
Makitie, Outi [1 ,2 ,3 ,9 ]
机构
[1] Folkhalsan Res Ctr, Genet Res Program, Helsinki, Finland
[2] Univ Helsinki, Childrens Hosp, Helsinki, Finland
[3] Univ Helsinki, Res Program Clin & Mol Metab, Helsinki, Finland
[4] Tampere Univ, Tampere Ctr Child Adolescent & Maternal Hlth Res, Tampere, Finland
[5] Tampere Univ Hosp, Dept Pediat, Tampere, Finland
[6] Tampere Univ Hosp, Dept Clin Genet, Tampere, Finland
[7] Duodecim Med Publicat Ltd, Helsinki, Finland
[8] Finland & Univ Tampere, Tampere Univ Hosp, Dept Pediat Neurol, Tampere, Finland
[9] Karolinska Univ Hosp, Karolinska Inst & Clin Genet, Dept Mol Med & Surg, Stockholm, Sweden
来源
HORMONE RESEARCH IN PAEDIATRICS | 2024年
基金
芬兰科学院;
关键词
Pleckstrin homology domain interacting protein; Early-onset obesity; Developmental delay; Chung-Jansen syndrome; Exome sequencing; DOMAIN;
D O I
10.1159/000542205
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Severe childhood obesity can be caused by pathogenic variants in several genes involved in monogenic and syndromic obesity. Recently, heterozygous variants in pleckstrin homology domain interacting protein (PHIP) have been identified in patients with obesity as part of Chung-Jansen syndrome. Case Presentation: The index patient is a 5-year-old boy with severe obesity since 1 year of age, developmental delay, facial dysmorphism, and behavior problems. Whole-exome sequencing identified a novel missense variant in PHIP (c.3182C>A, p.Ala1061Glu) in the index patient. Further genetic testing in family members revealed segregation of the same PHIP variant in the brother and mother, who both presented with severe childhood obesity and developmental delay or learning difficulties. The PHIP missense variant was predicted pathogenic by multiple in silico tools and affects a highly conserved residue. Conclusion: Early-onset obesity may be monogenic. Our finding expands the spectrum of disease-causing variants in PHIP and demonstrates variable intrafamilial clinical expressivity and severity. Screening for PHIP variants should be included in genetic testing in patients with severe early-onset obesity.
引用
收藏
页数:8
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