Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients

Hamad, Asma; Sherlaw-Sturrock, Charlotte; Glover, Kate; Salmon, Rachel; Low, Karen; Nair, Ramya; Sansbury, Francis H.; Rawlins, Lettie E; Carmichael, Jenny; Horton, Rachael; Wedderburn, Sarah; Edgerley, Katherine; Irving, Rachel; Callaghan, Mary; Mercer, Catherine H; McGowan, Ruth; Roberts, Leema; Titheradge, Hannah; Naik, Swati

doi:10.1016/j.ejmg.2023.104714

European Journal of Medical Genetics

2023

DOI: 10.1016/j.ejmg.2023.104714

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Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients

Asma Hamad

Charlotte Sherlaw-Sturrock

Kate Glover

et al.

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2024

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Cited by 3 publications

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Application of Genetic Origin Analysis of Copy Number Variations in Non‐Invasive Prenatal Testing

Wang,

Zhu,

Cui

et al. 2024

Prenatal Diagnosis

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ObjectiveThis study aimed to assess the application of origin analysis of copy number variations (CNVs) in non‐invasive prenatal testing (NIPT) and provide a basis for expanding the clinical application of NIPT.MethodWe enrolled 35,317 patients who underwent NIPT between January 2019 and March 2023. Genome sequencing of copy number variation (CNV‐Seq) analysis was performed using the CNV calling pipeline to identify subchromosomal abnormalities in maternal plasma. Genetic origin was determined by comparing the chimaerism ratio of CNV and the concentration of cell‐free foetal DNA (cffDNA). All pregnant women with a high risk of CNV, as indicated by the NIPT, were informed of their genetic origins. Amniocentesis was recommended for detecting the CNVs in foetal chromosomes, and pregnancy outcomes were tracked.ResultsA total of 109 pregnancies showed clinically significant positive results for CNV after NIPT, including 65 cases of maternal/foetal (M/F)‐CNVs and 44 cases of F‐CNVs. The occurrence of M/F‐CNVs was independent of age, screening (serological or ultrasound) indications for abnormalities, and mode of pregnancy. The incidence of pathogenic/likely pathogenic (P/LP)‐F‐CNVs was high in cases where serological screening indicated intermediate, high‐risk, or abnormal US findings (p < 0.05). In the M/F‐CNV group, most of the P/LP‐CNVs were small fragments with low penetrance; 55 (84.62%) were less than 5 Mb in size, and nine (13.85%) were between 5 and 10 Mb. In the F‐CNV group, foetal P/LP‐CNV was detected in 36 of 42 cases undergoing prenatal diagnosis, and no significant bias was noted in the size distribution of P/LP‐F‐CNV fragments. The prenatal diagnostic rate and positive predictive value in the F‐CNV group were 95.45% and 85.71%, respectively, which were significantly different from those in the M/F group (26.15% and 52.95%), respectively (p < 0.05).ConclusionsGenetic origin analysis of CNV can effectively improve adherence to prenatal diagnosis in pregnant women and the accuracy of prenatal diagnosis.

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Application of Genetic Origin Analysis of Copy Number Variations in Non‐Invasive Prenatal Testing

Wang,

Zhu,

Cui

et al. 2024

Prenatal Diagnosis

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Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders

Türkyılmaz,

Sağer,

Caliskan

et al. 2024

Mol Syndromol

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Introduction: Copy number variation (CNV) is the difference in the sequence of genomic segments, which can vary from one kilobase to several megabases. Certain CNVs have been linked to various human disorders, such as intellectual disability, multiple congenital anomalies, autism spectrum disorders, neurodegenerative and neuropsychiatric conditions, and cancer. The present study aims to classify brain magnetic resonance imaging (MRI) findings, describe neurological manifestations, and discuss the findings within the context of genotype–phenotype correlations in a cohort of patients with recurrent and nonrecurrent CNVs. Methods: A total of 21 patients with pathogenic CNV detected using microarray analysis were included in the study. Results: Analysis of the clinical findings of the patient cohort showed that 16 (76%) had microcephaly, 14 had epilepsy (66%), 20 had facial dysmorphism (95%), and all had developmental delay (100%). Novel brain MRI findings were detected in six (6/13, 46%) patients with recurrent CNV and five (5/8, 63%) patients with nonrecurrent CNV. Conclusion: CNV-related disorders should be considered in the differential diagnosis of patients with brain MRI findings suspicious for metabolic disorders. Brain MRI differences in patients with the same chromosomal deletion can be explained by the second-hit hypothesis. Additional single nucleotide variations and epigenetic factors in these cases may have led to the involvement of different regions of the brain. Revealing the phenotypic and genotypic characteristics of cases in rare disorders will contribute to the widespread use of precision medicine and genetic treatment approaches in the near future.

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Prenatal diagnosis and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome

Zhao,

Song,

Zhang

et al. 2024

Front. Genet.

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BackgroundThe clinical phenotypes of 16p13.11 microduplication syndrome have been extensively reported in previous studies, mostly about adults and children, with limited information available on fetal cases. This study aims to explore the genotype-phenotype correlation of fetuses with 16p13.11 microduplication syndrome and analyze the characteristics of prenatal diagnosis indications and provide clinical information for prenatal and postnatal genetic counseling.MethodsWe conducted a retrospective analysis of 3,451 pregnant women who underwent invasive prenatal diagnosis for SNP array between January 2018 and December 2022 at the Jinan Maternal and Child Health Hospital. Descriptive statistical analysis was performed on the prenatal diagnosis indications, pedigree analysis, pregnancy outcomes and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome.ResultsSNP array revealed that 15 fetuses had duplications in the 16p13.11 region with varying prenatal diagnosis indications. Among the cases, 6/15 exhibited ultrasound abnormalities, 5/15 had abnormal chromosomal copy number variations as indicated by non-invasive prenatal testing (NIPT), one case involved advanced maternal age, and 3/15 had other abnormalities. 16p13.11 microduplication syndrome was closely related to ultrasound abnormalities, especially structural abnormalities and soft marker anomalies (abnormal ultrasonic soft indicators), while the indication of NIPT could improve the detection rate of copy number variations (CNVs) in this region. Only 7/15 fetuses underwent pedigree verification, with one case of de novo 16p13.11 microduplication, and the others inherited from one parent. Pregnancy was terminated in 2/15 cases and the outcome of one case is unknown due to loss to follow-up. Among the remaining cases, only one case exhibited a ventricular septal defect, while another presented with omphalocele. No other obvious abnormalities were reported postnatally.ConclusionThe prenatal phenotypes of fetuses with 16p13.11 microduplication were highly associated with ultrasound abnormalities but lacked specificity. Comprehensive genetic tracing, outcome analysis, and follow-up are essential for providing accurate prenatal and postnatal genetic counseling.

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Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients

Cited by 3 publications

References 15 publications

Application of Genetic Origin Analysis of Copy Number Variations in Non‐Invasive Prenatal Testing

Application of Genetic Origin Analysis of Copy Number Variations in Non‐Invasive Prenatal Testing

Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders

Prenatal diagnosis and postnatal follow-up of 15 fetuses with 16p13.11 microduplication syndrome

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