Clinical characteristics of BRAT1-related disease: a systematic literature review

Background: BRAT1 (BRCA1-associated ataxia telangiectasia mutated activator 1) is involved in many important biological processes, including DNA damage response and maintenance of mitochondrial homeostasis. Dysfunctional BRAT1 causes variable clinical phenotypes, which hinders BRAT1-related disease from recognition and diagnosis.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was the guideline for this systematic review. MEDLINE was searched by terms ("BAAT1" and "BRAT1") from inception until June 21, 2022.

Results: Twenty-eight studies, screened out of 49 records, were included for data extraction. The data from fifty patients with mutated BRAT1 were collected. There are 3 high relevant phenotypes, 4 medium relevant phenotypes and 3 low relevant phenotypes. Eye-related abnormal features were most frequently reported: 27 abnormal features were observed. Thirty-nine kinds of pathogenic nucleotide change in BRAT1 were reported. Top three common mutations of BRAT1 were c.638_639insA (16 cases), c.1395G > A (5 cases) and c.294dupA (4 cases). Homozygous mutations in BRAT1 presented a more severe phenotype than those who are compound heterozygotes.

Conclusions: This is the first comprehensive systematic review to present quantitative data about clinical characteristics of BRAT1-related disease, which helps doctors to recognize and diagnose it easier.