The Power of Clinical Diagnosis for Deciphering Complex Genetic Mechanisms in Rare Diseases

被引：4

作者：

Shu, Li ^{[1
,2
,3
,4
]}

Maroilley, Tatiana ^{[1
,2
,3
,4
]}

Tarailo-Graovac, Maja ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calgary, Cumming Sch Med, Dept Biochem, Calgary, AB T2N 4N1, Canada

[2] Univ Calgary, Cumming Sch Med, Dept Mol Biol, Calgary, AB T2N 4N1, Canada

[3] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB T2N 4N1, Canada

[4] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary, AB T2N 4N1, Canada

来源：

GENES | 2023年 / 14卷 / 01期

关键词：

clinical diagnosis; rare disease; complex mechanism; structural variants; non-coding variants; DIGENIC INHERITANCE; MEDIATED DELETION; REPEAT EXPANSION; VARIANTS; MUTATIONS; GENOMICS; IDENTIFICATION; SPECTRUM; REGION;

D O I：

10.3390/genes14010196

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Complex genetic disease mechanisms, such as structural or non-coding variants, currently pose a substantial difficulty in frontline diagnostic tests. They thus may account for most unsolved rare disease patients regardless of the clinical phenotype. However, the clinical diagnosis can narrow the genetic focus to just a couple of genes for patients with well-established syndromes defined by prominent physical and/or unique biochemical phenotypes, allowing deeper analyses to consider complex genetic origin. Then, clinical-diagnosis-driven genome sequencing strategies may expedite the development of testing and analytical methods to account for complex disease mechanisms as well as to advance functional assays for the confirmation of complex variants, clinical management, and the development of new therapies.

引用

页数：17

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