Trujillano Laura, Valenzuela Irene, Costa-Roger Mar, Cuscó Ivon, Fernandez-Alvarez Paula, Cueto-González Anna, Lasa-Aranzasti Amaia, Masotto Bárbara, Abulí Anna, Codina-Solà Marta, Del Campo Miguel, Ruiz Moreno Juan Antonio, Pardo Domínguez Cristina, Palma Milla Carmen, Pérez de la Fuente Rubén, Quesada-Espinosa Juan Francisco, Núñez-Enamorado Noemí, Gener Blanca, Ballesta-Martínez María Juliana, Brea-Fernández Alejandro J, Fernández-Prieto Montse, Trujillo-Quintero Juan Pablo, Ruiz Anna, Santos-Simarro Fernando, Rosello Mónica, Orellana Carmen, Martinez Francisco, Martinez-Monseny Antonio F, Casas-Alba Dídac, Serrano Mercedes, Palomares-Bralo María, Rikeros-Orozco Emi, Gómez-Cano María Ángeles, Tirado-Requero Pilar, Pié Juste Juan, Ramos Feliciano J, García-Arumí Elena, Tizzano Eduardo F
Clinical and Molecular Genetics Area, Vall d'Hebron Hospital, Medicine Genetics Group, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Genetics Department, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Clin Genet. 2025 Jun;107(6):646-662. doi: 10.1111/cge.14701. Epub 2025 Jan 20.
Bainbridge-Ropers Syndrome (BRPS) is a genetic condition resulting from truncating variants in the ASXL3 gene. The clinical features include neurodevelopmental and language impairments, behavioral issues, hypotonia, feeding difficulties, and distinctive facial features. In this retrospective study, we analyzed 22 Spanish individuals with BRPS, aiming to perform a detailed clinical and molecular description and establish a genotype-phenotype correlation. We identified 19 ASXL3 variants, nine of which are novel. We documented recurrence in nontwin siblings due to parental mosaicism. The predominant prenatal finding was intrauterine growth restriction (35%) followed, after birth, by feeding difficulties (90.5%), hypotonia (85.7%), and gastroesophageal reflux disease (82.4%). Later in life, intellectual disability, language impairment, autism spectrum disorder (75%), and joint laxity (73.7%) were noted. Individuals with variants in the 3' mutational cluster region (MCR) of exon 12 exhibited more perinatal feeding problems, and those with variants in the 5' MCR of exon 11 displayed lower percentiles in height and occipitofrontal circumference, as well as higher frequency of arched eyebrows. This study is the first characterization of a Spanish BRPS cohort, with more than 50 clinical features analyzed, representing the most detailed phenotypic analysis to date.
班布里奇-罗佩斯综合征（BRPS）是一种由ASXL3基因截短变异导致的遗传性疾病。其临床特征包括神经发育和语言障碍、行为问题、肌张力减退、喂养困难以及独特的面部特征。在这项回顾性研究中，我们分析了22名患有BRPS的西班牙人，旨在进行详细的临床和分子描述，并建立基因型-表型相关性。我们鉴定出19种ASXL3变异，其中9种是新发现的。我们记录了由于父母嵌合体导致非双胞胎兄弟姐妹出现复发的情况。主要的产前发现是宫内生长受限（35%），出生后依次为喂养困难（90.5%）、肌张力减退（85.7%）和胃食管反流病（82.4%）。在生命后期，发现有智力残疾、语言障碍、自闭症谱系障碍（75%）和关节松弛（73.7%）。外显子12的3'突变簇区域（MCR）有变异的个体表现出更多围产期喂养问题，而外显子11的5' MCR有变异的个体身高和枕额周长百分位数较低，且挑眉频率较高。本研究是对西班牙BRPS队列的首次特征描述，分析了50多种临床特征，是迄今为止最详细的表型分析。
