Journal of Clinical Pediatrics >
Clinical characteristics and genetic analysis of a case of developmental delay caused by CHD1 gene variation
Received date: 2024-01-09
Accepted date: 2024-07-30
Online published: 2025-01-03
Objective To explore the clinical features and genetic mutation characteristics of a case of global developmental delay caused by a novel variant in the CHD1 gene, and to investigate its relationship with Pilarowski- Bjornsson syndrome (PILBOS, OMIM# 617682). Method Trio whole-exome sequencing (trio-WES) was performed to identify the pathogenic gene within the pedigree, and the clinical data of the patient were summarized to analyze both clinical and genetic characteristics. Result The patient was an 8-month-old male and presented to the Department of Pediatric Neurology at our hospital with the main complaint of " developmental delay for more than six months". Trio-WES detection revealed a missense mutation in exon 1 of the CHD1 gene on chromosome 5q15-q21, with a c.13A>G (p.Ser5Gly) mutation (transcript number NM_001270), which represented a novel (de novo) variation consistent with an autosomal dominant inheritance pattern. The final diagnosis was" Comprehensive developmental delay caused by CHD1 gene deficiency". Conclusion There are currently few reports on cases of CHD1 gene mutations, and the identified mutations in this case has not been previously documented. Expanding the genotype phenotype spectrum of CHD1 gene defects also provides data for further understanding of PILBOS disease. Accurate diagnosis relies on molecular genetic testing, and additional cases need to be accumulated for further analysis of genotype phenotype relationships and prognosis evaluation.
CHEN Hao , LI Xiao , LI Lin , GUAN Jing , DONG Yan , ZHANG Xiaoli , DU Kaixian . Clinical characteristics and genetic analysis of a case of developmental delay caused by CHD1 gene variation[J]. Journal of Clinical Pediatrics, 2025 , 43(1) : 45 -49 . DOI: 10.12372/jcp.2025.24e0015
[1] | Pilarowski GO, Vernon HJ, Applegate CD, et al. Missense variants in the chromatin remodeler CHD1 are associated with neurodevelopmental disability[J]. J Med Genet, 2018, 55(8): 561-566. |
[2] | Zepeda-Mendoza C, Goodenberger ML, Kuhl A, et al. Familial segregation of a 5q15-q21.2 deletion associated with facial dysmorphism and speech delay[J]. Clin Case Rep, 2019, 7(6): 1154-1160. |
[3] | Lusser A, Urwin DL, Kadonaga JT. Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly[J]. Nat Struct Mol Biol, 2005, 12(2): 160-166. |
[4] | Kim MS, Chung NG, Kang MR, et al. Genetic and expressional alterations of CHD genes in gastric and colorectal cancers[J]. Histopathology, 2011, 58(5): 660-668. |
[5] | Flanagan JF, Mi LZ, Chruszcz M, et al. Double chromodomains cooperate to recognize the methylated histone H3 tail[J]. Nature, 2005, 438(7071): 1181-1185. |
[6] | Woodage T, Basrai MA, Baxevanis AD, et al. Characterization of the CHD family of proteins[J]. Proc Natl Acad Sci U S A, 1997, 94(21): 11472-11477. |
[7] | Konev AY, Tribus M, Park SY, et al. CHD1 motor protein is required for deposition of histone variant H3.3 into chromatin in vivo[J]. Science, 2007, 317(5841): 1087-1090. |
[8] | Simic R, Lindstrom DL, Tran HG, et al. Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes[J]. EMBO J, 2003, 22(8): 1846-1856. |
[9] | Lin JJ, Lehmann LW, Bonora G, et al. Mediator coordinates PIC assembly with recruitment of CHD1[J]. Genes Dev, 2011, 25(20): 2198-2209. |
[10] | Sims RJ 3rd, Millhouse S, Chen CF, et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing[J]. Mol Cell, 2007, 28(4): 665-676. |
[11] | Al-Aamri M, Alshaqaq M, Al-Abdi SY. A Saudi girl with co-occurring CHD1 (Pilarowski-Bjornsson syndrome) and ASH1L gene variants[J]. Cureus, 2023, 15(12): e49905 |
[12] | Sunwoo Y, Seo S H, Kim HJ, et al. Variant of CHD1 gene resulting in a Korean case of Pilarowski-Bjornsson syndrome[J]. Journal of Genetic Medicine, 2022, 19(2): 111-114. |
[13] | 赵少志, 段红芳, 杜囡, 等. 应用CNV-seq鉴定染色体新发不平衡易位一例[J]. 中华医学遗传学杂志, 2020, 37(9): 1053-1054. |
Zhao SZ, Duan HF, Du N, et al. Application of CNV-seq to identify a new case of chromosomal imbalanced translocation[J]. Zhonghua Yixue Yichuan Zazhi, 2020, 37 (9): 1053-1054. | |
[14] | Wyatt BH, Raymond TO, Lansdon LA, et al. Using an aquatic model, Xenopus laevis, to uncover the role of chromodomain 1 in craniofacial disorders[J]. Genesis, 2021, 59(1-2): e23394. |
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