Genetic analysis of an X-linked intellectual disability pedigree

VernacularTitle:X染色体连锁智力障碍1家系遗传学分析
Author: Cuiyun LI ¹ ; Tian'e CAI ¹ ; Man LIN ¹ ; Ruen YAO ¹ ; Wei LI ¹ ; Xiaoyan LIN ¹ ; Weimei XING ¹ ; Ying YU ¹
Author Information

1. 上海交通大学医学院附属上海儿童医学中心海南医院医学遗传与产前诊断中心，三亚　572000
Publication Type:Journal Article
Keywords: Intellectual disability; Xp22.2p22.11 microduplication; Prenatal diagnosis; RPS6KA3 gene; X chromosome inactivation
From: Chinese Journal of Perinatal Medicine 2025;28(9):775-778
CountryChina
Language:Chinese
Abstract: This study presents prenatal diagnosis and genetic analysis of a pedigree with X-linked intellectual disability. A gravida at approximately 20 gestational weeks underwent prenatal diagnosis following non-invasive prenatal testing suggested sex chromosome abnormalities. Copy number variation (CNV) sequencing identified a 5.7 Mb duplication at Xp22.2p22.11 in the fetus, which initially classified as a variant of uncertain clinical significance. This duplication was inherited from the phenotypically normal mother, while paternal CNV results were normal. Genetic testing of four intellectually disabled family members revealed the identical 5.7 Mb duplication. Through expanded pedigree analysis, the pathogenicity classification of the Xp22.2p22.11 microduplication was upgraded to likely pathogenic. After comprehensive genetic counseling, the family elected pregnancy termination with informed consent.