Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency and MECP2 duplication syndrome
10.3760/cma.j.cn511374-20221110-00780
- VernacularTitle:罕见鸟氨酸氨基甲酰转移酶缺乏症合并MECP2重复综合征一个家系的基因变异分析及产前诊断
- Author:
Qinghua ZHANG
1
;
Shengju HAO
;
Ling HUI
;
Lei ZHENG
;
Xing WANG
;
Xuan FENG
;
Furong LIU
;
Xue CHEN
;
Bingbo ZHOU
;
Yupei WANG
;
Chuan ZHANG
Author Information
1. 甘肃省妇幼保健院（甘肃省中心医院）医学遗传中心，兰州 730050
- Keywords:
Hyperammonemia;
Ornithine carbamoyltransferase deficiency;
OTC gene;
Prenatal diagnosis;
Copy number variation;
MECP2 duplication syndrome
- From:
Chinese Journal of Medical Genetics
2024;41(3):306-311
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.Methods:A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.Results:The proband, a 3-day-old female, was found to harbor heterozygous deletion of exons 7-9 of the OTC gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4). The proband was diagnosed with OTCD, which was in keeping with her acute encephalopathy and metabolic abnormalities (manifesting as hyperammonemia, decreased blood citrulline, and increased urine orotic acid). Prenatal diagnosis was carried out for the subsequent pregnancy. The fetus did not harbor the exons 7-9 deletion of the OTC gene, but was found to carry a duplication in Xq28 region (which encompassed the whole region of MECP2 duplication syndrome) and was positive for the SRY sequence. The same duplication was also found in the proband and her mother. Considering the possible existence of X-chromosome inactivation, the proband was diagnosed with two X-linked recessive disorders including OTCD and MECP2 duplication syndrome, and the fetus was determined as a male affected with the MECP2 duplication syndrome. Conclusion:Discoveries of the pathogenic variants underlying the OTCD and MECP2 duplication syndrome have enabled clinical intervention, treatment, genetic counseling and prenatal diagnosis for this pedigree.
