Abstract:

Objective: To analyze the clinical and genetic characteristics of 1q21.1 distal microdeletion/microduplication syndrome combined with congenital heart disease (CHD) using chromosome copy number variation sequencing (CNV-seq). Methods: Retrospective analysis was conducted on the four pediatric patients diagnosed with 1q21.1 microdeletion/microduplication syndrome and CHD using CNV-seq at Gansu Provincial Maternity and Child Care Hospital. Results: The chromosomal CNV overlap region of 4 cases was identified as chr1:g.1465200000-147840000, the heart-related genes included CAJ5, CAJ8, PPKAB2, CHD1L, BCL9, etc. One child with microduplication displayed various concurrent anomalies including micromandible malformations, retrolingual fall, maxillary clefts as well as aberrant urinary system development. In three children with microdeletion, two out of three experienced significant growth retardation (one presenting severe intellectual impairment along with hypotonia and micropenis while another exhibited distinctive facial features), and one child underwent surgery for CHD during follow-up with a favorable prognosis. Conclusions: CHD in combination with developmental delay and/or distinctive facial features, represents a significant phenotype in young children affected by 1q21.1 microdeletion/duplication syndrome. It is imperative to identify chromosomal CNV in these individuals to provide theoretical basis for subsequent clinical diagnosis and treatment.

Key words: DNA copy number variations, Whole genome sequencing, Chromosome deletion, Chromosome duplication, Heart defects, congenital