Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review.

BACKGROUND: Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1. CASE PRESENTATION: We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis. CONCLUSION: A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.

Identification of 1q21.1 microduplication in a family: A case report.

BACKGROUND: Copy number variation (CNV) has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research. 1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders, autism spectrum disorders, congenital malformations, and congenital heart defects with genetic heterogeneity. CASE SUMMARY: We reported a pediatric patient with 1q21.1 microduplication syndrome, and carried out a literature review to determine the correlation between 1q21.1 microduplication and its phenotypes. We summarized the patient's medical history and clinical symptoms, and extracted genomic DNA from the patient, her parents, elder brother, and sister. The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period. Whole exon sequencing and whole genome low-depth sequencing (CNV-seq) were then performed. Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region, which was located in the 1q21.1 region. Family analysis showed that the pathogenetic duplication fragment, which was also detected in her elder brother's DNA originated from the mother. CONCLUSION: Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome, which is of great significance for genetic counseling and early intervention.

Case Report: Identification of a de novo Microdeletion 1q44 in a Patient With Seizures and Developmental Delay.

Objective: 1q44 microdeletion syndrome is difficult to diagnose due to the wide phenotypic spectrum and strong genetic heterogeneity. We explore the correlation between the chromosome microdeletions and phenotype in a child with 1q44 microdeletion syndrome, we collected the clinical features of the patient and combined them with adjacent copy number variation (CNV) regions previously reported. Methods: We collected the full medical history of the patient and summarized her clinical symptoms. Whole-exome sequencing (WES) and CapCNV analysis were performed with DNA extracted from both the patient's and her parents' peripheral blood samples. Fluorescent quantitative PCR (q-PCR) was performed for the use of verification to the CNV regions. Results: A 28.7 KB microdeletion was detected in the 1q44 region by whole-exome sequencing and low-depth whole-genome sequencing. The deleted region included the genes COX20 and HNRNPU. As verification, karyotype analysis showed no abnormality, and the results of qPCR were consistent with that of whole-exome sequencing and CapCNV analysis. Conclusion: The patient was diagnosed with 1q44 microdeletion syndrome with clinical and genetic analysis. Analyzing both whole-exome sequencing and CapCNV analysis can not only improve the diagnostic rate of clinically suspected syndromes that present with intellectual disability (ID) and multiple malformations but also support further study of the correlation between CNVs and clinical phenotypes. This study lays the foundation for the further study of the pathogenesis of complex diseases.