Clinical characteristics of patients with SALL1-related disorder.

IF 2.6 3区 医学 Q1 PEDIATRICS
Pediatric Nephrology Pub Date : 2025-11-01 Epub Date: 2025-07-14 DOI:10.1007/s00467-025-06878-z
Yoshitaka Asagai, Yu Tanaka, Hiroaki Hanafusa, China Nagano, Tomoko Horinouchi, Shingo Ishimori, Hiroshi Kaito, Kazumoto Iijima, Kandai Nozu, Naoya Morisada
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引用次数: 0

Abstract

Background: The Spalt-like transcription factor 1 (SALL1) gene is essential for kidney development. Pathogenic SALL1 variants cause Townes-Brocks syndrome 1 (TBS1), which typically presents with imperforate anus, dysplastic ears, and digital anomalies. However, clinical features vary widely. Some patients present only with dysplastic ears and hearing loss (HL) or with congenital anomalies of the kidney and urinary tract (CAKUT), resembling branchio-oto-renal syndrome (BORS), a presentation referred to as Townes-Brocks branchio-oto-renal-like (TBS BOR-like) syndrome. In this study, we aimed to describe the clinical characteristics of patients with SALL1-related disorders in the Japanese population.

Methods: We analyzed phenotypes of a nationwide cohort comprising 1108 families with chronic kidney disease (CKD) or mild urinary anomalies, using genetic testing conducted from 2010 to 2024.

Results: We identified SALL1 variants in 14 families (20 individuals): seven frameshift, four nonsense, one missense, one exon 2 deletion, and one whole-gene deletion. Ten variants were novel. The median age at diagnosis was 16 years (male:female = 13:7). Dysplastic ears were observed in 45%, HL in 40%, digital anomalies in 40%, and anorectal malformations in 25%. Based on clinical features, eight individuals were diagnosed with TBS1, four with TBS BOR-like syndrome, and seven with non-syndromic CAKUT. One case lacked detailed clinical data. Most variants were truncating and located in exon 2.

Conclusions: SALL1-related disorders exhibit broad phenotypic variability. Some cases present with atypical features overlapping with TBS BOR-like syndrome or isolated CAKUT, rather than with typical TBS1. These findings enhance the understanding and diagnosis of SALL1-related disorders.

sall1相关疾病患者的临床特征。
背景:spalt样转录因子1 (SALL1)基因对肾脏发育至关重要。致病性SALL1变异引起汤斯-布罗克斯综合征1 (TBS1),其典型表现为肛门闭锁,耳朵发育不良和数字异常。然而,临床特征差异很大。一些患者仅表现为发育不良的耳朵和听力损失(HL)或先天性肾脏和尿路异常(CAKUT),类似于分支-耳-肾综合征(BORS),这种表现被称为towns - broks分支-耳-肾样(TBS - BOR-like)综合征。在这项研究中,我们旨在描述日本人群中sall1相关疾病患者的临床特征。方法:我们分析了全国1108个慢性肾脏疾病(CKD)或轻度泌尿异常家庭的表型,使用2010年至2024年进行的基因检测。结果:我们在14个家族(20个个体)中鉴定出SALL1变异:7个移码、4个无义、1个错义、1个外显子2缺失和1个全基因缺失。有10种变体是新颖的。诊断时的中位年龄为16岁(男性:女性= 13:7)。耳发育不良占45%,HL占40%,指畸形占40%,肛肠畸形占25%。根据临床特征,8人被诊断为TBS1, 4人被诊断为TBS or样综合征,7人被诊断为非综合征性CAKUT。1例缺乏详细的临床资料。大多数变异是截断的,位于外显子2。结论:sall1相关疾病表现出广泛的表型变异性。一些病例表现出与TBS bor样综合征或孤立性CAKUT重叠的非典型特征,而不是典型的TBS1。这些发现增强了对sall1相关疾病的认识和诊断。
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来源期刊
Pediatric Nephrology
Pediatric Nephrology 医学-泌尿学与肾脏学
CiteScore
4.70
自引率
20.00%
发文量
465
审稿时长
1 months
期刊介绍: International Pediatric Nephrology Association Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.
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