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Background: With the extensive use of chromosomal microarray analysis (CMA), an increasing number of variants of uncertain significance (VOUS) have been detected. The objective of the present study was to elucidate the pathogenicity and clinical variability associated with isolated recurrent 4q35.2 microduplications within the Chinese population. Methods: The present study involved 14 cases of isolated recurrent 4q35.2 microduplication (including 12 fetuses and 2 cases of pediatric patients) out of 5,188 subjects who sought genetic consultation at our hospital and received CMA detection. WES technology was subsequently utilized to identify additional sequence variants in a patient with multiple clinical anomalies. Results: All 14 cases exhibited isolated recurrent 4q35.2 microduplications spanning a 1.0-Mb region encompassing the ZFP42 gene. Among the 12 fetuses, 11 displayed normal clinical features, while one was born with renal duplication and hydronephrosis. Additionally, in the two pediatric patients, WES was performed for Case 1, who presented with congenital cataracts, severe intellectual disability, and seizures. This patient inherited the 4q35.2 microduplication from his phenotypically normal mother. WES identified a novel NM_000276:c.2042G > T (p.G681V) variant in the OCRL gene, which is associated with Lowe syndrome and may account for the observed phenotypic variability within this family. Conclusion: A series of 14 cases with isolated recurrent 4q35.2 microduplications were investigated, highlighting a potential association with increased susceptibility to renal abnormalities. Further, the present findings may expand the mutation spectrum of the OCRL gene associated with Lowe syndrome and provide valuable insights for the genetic etiological diagnosis of patients with unexplained copy number variants. [ABSTRACT FROM AUTHOR]

Background: Limited research has been conducted regarding the elucidation of genotype–phenotype correlations within the 20q13.33 region. The genotype–phenotype association of 20q13.33 microdeletion remains inadequately understood. In the present study, two novel cases of 20q13.33 microdeletion were introduced, with the objective of enhancing understanding of the genotype–phenotype relationship. Methods: Two unrelated patients with various abnormal clinical phenotypes from Fujian province Southeast China were enrolled in the present study. Karyotype analysis and chromosomal microarray analysis (CMA) were performed to investigate chromosomal abnormalities and copy number variants. Results: The results of high‐resolution G‐banding karyotype analysis elicited a 46,XY,der(20)add(20)(q13.3) in Patient 1. This patient exhibited various clinical manifestations, such as global developmental delay, intellectual disability, seizures, and other congenital diseases. Subsequently, a 1.0‐Mb deletion was identified in the 20q13.33 region alongside a 5.2‐Mb duplication in the 14q32.31q32.33 region. In Patient 2, CMA results revealed a 1.8‐Mb deletion in the 20q13.33 region with a 4.8‐Mb duplication of 17q25.3. The patient exhibited additional abnormal clinical features, including micropenis, congenital heart disease, and a distinctive crying pattern characterized by a crooked mouth. Conclusion: In the present study, for the first time, an investigation was conducted into two novel cases of 20q13.33 microdeletion with microduplications in the 17q25.3 and 14q32.31q32.33 regions in the Chinese population. The presence of micropenis may be attributed to the 20q13.33 microdeletion, potentially expanding the phenotypic spectrum associated with this deletion. [ABSTRACT FROM AUTHOR]

Background: Pathogenic PAK1 variants were described to be causative of neurodevelopmental disorder with macrocephaly, seizures, and speech delay. Herein, we present a de novo PAK1 variant combine with a de novo terminal 1q microdeletion in a Chinese pediatric patient, aiming to provide more insights into the underlying genotype–phenotype relationship. Methods: Enrolled in this study was a 6-year-old girl with clinical features of global developmental delay, severe intellectual disability, speech delay, and seizures from Quanzhou region of China. Karyotype and chromosomal microarray analysis (CMA) were performed to detect chromosome abnormalities in this family. Whole exome sequencing (WES) was performed to investigate additional genetic variants in this family. Results: No chromosomal abnormalities were elicited from the entire family by karyotype analysis. Further familial CMA results revealed that the patient had a de novo 2.7-Mb microdeletion (arr[GRCh37] 1q44(246,454,321_249,224,684) × 1]) in 1q44 region, which contains 14 OMIM genes, but did not overlap the reported smallest region of overlap (SRO) responsible for the clinical features in 1q43q44 deletion syndrome. In addition, WES result demonstrated a de novo NM_002576: c.251C > G (p.T84R) variant in PAK1 gene in the patient, which was interpreted as a likely pathogenic variant. Conclusion: In this study, we identify a novel PAK1 variant associated with a terminal 1q microdeletion in a patient with neurodevelopmental disorder. In addition, we believe that the main clinical features may ascribe to the pathogenic variant in PAK1 gene in the patient. [ABSTRACT FROM AUTHOR]

Background: Isolated terminal 4q35.2 microdeletion is an extremely rare copy number variant affecting people all over the world. To date, researchers still have controversial opinions and results on its pathogenicity. Here, we aim to present a Chinese pediatric patient with terminal 4q35.2 microdeletion and use this case to clarify the underlying genotype–phenotype correlation. Methods: A 17-year-old boy from Quanzhou, South China, was recruited as the main subject in this study. Karyotype and single-nucleotide polymorphism (SNP) based microarray analysis were carried out to detect chromosomal abnormalities and copy number variants in this family. Trio whole exome sequencing (Trio-WES) was performed to investigate the potential pathogenic variant in this family. Results: During observation, we identified abnormal clinical phenotypes including upper eyelid ptosis, motor developmental delay, abnormal posturing, abnormality of coordination, attention deficit hyperactivity disorder, and involuntary movements in the patient. SNP array analysis results confirmed a case of 2.0 Mb 4q35.2 microdeletion and parental SNP array verification results indicated that the terminal 4q35.2 microdeletion was inherited from his mother. No copy number variants were detected in his father. In addition, the trio-WES results demonstrated none of pathogenic or likely pathogenic variants in the patient. Conclusions: This study brings a novel analysis of a case of 2.0 Mb terminal 4q35.2 microdeletion affecting a Chinese individual. In addition, additional clinical symptoms such as upper eyelid ptosis and involuntary movements were first reported to affect a patient with terminal 4q35.2 microdeletion, which may broaden the phenotype spectrum of the condition. [ABSTRACT FROM AUTHOR]