16q24.3 Microdeletions Disrupting Upstream Non-Coding Region of ANKRD11 Cause KBG Syndrome

Genes · 2025-01-24 · 1 citations

Background: KBG syndrome is a multisystem developmental disorder characterized by macrodontia of the upper permanent incisors, distinctive facial features, a short stature, developmental delay, variable intellectual disability, and behavioral issues. Heterozygous chromosomal deletion encompassing the partial or entire ANKRD11 gene, as well as the loss of function mutations, result in haploinsufficiency of the gene, leading to KBG syndrome. This indicates that precise levels of ANKRD11 transcripts or protein are essential for human development. Clinical report: Here, we report three individuals who present with clinical features of KBG syndrome. These individuals carry microdeletions encompassing only the non-coding exon 1 of ANKRD11 and its upstream region. Our molecular analysis showed that this deletion leads to reduction in the ANKRD11 transcript and global transcriptome alterations similar to those seen in KBG syndrome patients. Conclusions: We concluded that microdeletions involving non-coding exon 1 of ANKRD11 lead to KBG syndrome. Our study suggests the utility of transcriptome analysis in aiding the interpretation of novel copy number variants in the non-coding genomic region of ANKRD11.

Correction: Clinical impact of pharmacogenomics in pediatric care: insights extracted from clinical exome sequencing

Frontiers in Genetics · 2025-07-08

Correction: Clinical impact of pharmacogenomics in pediatric care: insights extracted from clinical exome sequencing* Correspondence: simran.maggo@su.eduKeywords: same as original articleCorrection on: Maggo, S., et al. (2025). "Clinical impact of pharmacogenomics in pediatric care: insights extracted from clinical exome sequencing." Frontiers in Genetics Volume 16 - 2025. https://doi.org/10.3389/fgene.2025.1574325Error in figure/tableIn the published article, there was an error in Table 1 as published. Table one, included two instances of SLCO1B1 The first instance should be CYP2B6. The corrected Table1 and its caption appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Isolated lateralized overgrowth and the need for tumor screening: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Genetics in Medicine · 2025-07-22

Survival of an Infant With PTPRQ Deletion With Congenital Absence of the Anterior Chest Wall

American Journal of Respiratory and Critical Care Medicine · 2025-05-01

Abstract Introduction: There are a limited number of reported cases of children born with anterior chest wall defects and management of these patients is undefined. Here we present a newborn with anterior chest wall anomalies and our current considerations for long-term treatment. Case Presentation: This is a 7-month-old male born at 34 weeks with absence of the anterior ribs leading to acute respiratory failure requiring mechanical ventilation. Chest CT demonstrates transverse rib cage widening due to non-curvature and lateral out-splaying of the ribs. Despite mechanical ventilatory support he continued to have hypoxemia and hypercapnia, likely secondary to the absence of chest wall recoil and the inability to generate negative intrapleural pressure. He underwent tracheostomy for long-term ventilation management at one month of age. Genetic evaluation identified a homozygous deletion of PTPRQ gene which includes regions of the MYF5 and MYF6 genes. MYF5 and MYF6 are important in embryonic muscle development and play a key role in anterior rib morphogenesis. Disruption of MYF5 expression has been associated with rib and vertebral anomalies which is consistent with the patient's findings. At 7 months of age, he has fewer hypoxemic events and is able to tolerate minute range sprints from ventilator support. There is bilateral atelectasis and a reduced left lung volume, see Figure 1. Lung MRI acquired using ultrashort echo time (UTE) based sequences and chest CT demonstrate reduced left lung volume and bilateral atelectasis which was not present on his imaging at 10 days of age. A recent assessment using electrical impedance tomography (EIT) demonstrated significantly unequal regional ventilation, with 71% of tidal ventilation on the right side compared to 29% on the left. Further evaluation is being pursued to understand if asymmetric perfusion may be playing a role in his lung volume asymmetry. Currently, vertical expandable prosthetic titanium rib (VEPTR) placement is being considered when the patient reaches 9 to 12 months of age as well as negative pressure ventilation to reduce atelectasis. Discussion: Cases of congenital anterior chest wall anomalies due to genetic variation are extremely rare. We describe a case of an infant surviving with chronic mechanical ventilation despite severe anterior rib anomalies. He is demonstrating improvement, but his medical course is complicated by severe asymmetric lung volume. Hopefully by sharing these methods we can provide guidance for any future cases and ultimately increase the chance for survival for these patients.

Opioid-Related Pharmacogenomic Variants in a Retrospective Cohort of High-Risk Hospitalized Infants

The Journal of Pediatrics · 2025-07-17 · 1 citations

P564: Parental perspectives on pediatric genomic testing, research, and data management in a multicultural population

Genetics in Medicine Open · 2025-01-01

Contributors

Elsevier eBooks · 2025-06-02

P796: Vanishing copy number gains: causative chromosomal changes or unstable findings of unknown consequence?

Genetics in Medicine Open · 2025-01-01

Case Presentation: A four-month-old female presented with webbed neck, short stature, microcephaly, failure to thrive, dysmorphic facial features, cardiac murmur, ventricular septal defect, abnormal transaminases, and hematochezia.No clinical suspicion of differences of sex development (DSD) was noted.CMA testing was requested.Diagnostic Workup: A 1.9 Mb pathogenic deletion was identified at 7p22.2p22.1, which is the likely cause of this individual's phenotype.On the X chromosome, a 5.3 Mb terminal pathogenic deletion at Xq28 and a 2.6 Mb terminal duplication of Xp22.33 overlapping PAR1 was called by the analysis pipeline.Manual review of array data revealed the presence of Yp material which included the SRY gene.The chromosomal sex was predicted to be female by the analysis software, and the gain of Yp was not flagged.This is likely due to the PAR regions being displayed on the X chromosome, regardless of whether it originates from the X or Y chromosome.This suggests the PAR1 gain was from the Y chromosome indicative of a translocation.Karyotype analysis confirmed a derivative chromosome X from an X;Y translocation [46,X,der(X)t(X;Y)(q28;p11.2)].

Lipid transport is necessary for neocortical lamination

bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-09

ABSTRACT We previously described the Alkuraya-Kučinskas syndrome, a disorder associated with biallelic variants in BLTP1 (bridge-like lipid transfer protein), a.k.a. KIAA1109 . The majority of probands die perinatally with corpus callosum agenesis, ventriculomegaly and arthrogryposis. Homozygous ablation of mouse Bltp1 resulted in similar preweaning lethality. Here, we describe ten novel patients expanding the characterization of this syndrome at the mild end of the phenotypic spectrum. To model this syndrome, we engineered Emx1-Cre-mediated conditional knockouts (cKO) in which Bltp1 expression is only removed in cortical and hippocampal neurons. This restricted ablation of Bltp1 recapitulated the preweaning lethality observed in the constitutional knockouts, suggesting that lack of BLTP1 expression in neurons is sufficient to cause death. Homozygous cKO presented a complete agenesis of the corpus callosum, a smaller anterior commissure, a malformed hippocampus and a reduced thickness of the cortical plate with a complete lack of defined structural layers and absence of radial glial and intermediate neural progenitors and mature neurons. As BLTP1 was shown to be a barrel-shaped tube containing lipids, we compared the amount of lipid species in the cKO and their control littermates’ cortexes. We observed significant depletions of ether-linked phosphatidylethanolamines and triglycerides and accumulations of sphingomyelins and hexosylceramides in cKOs. Our results are consistent with the recent description of BLTP1 as a tubular protein that transports phospholipids between the endoplasmic reticulum and the plasma membrane. They suggest that non-vesicular lipid transport is essential for neocortical and cerebellar lamination. Consistent with a BLTP1 role in cortex development we show that heterozygous carriers of a BLTP1 truncation variant presented a decrease in peripheral cortical grey matter suggesting an autosomal dominant inheritance pattern beside the already described autosomal recessive.

Autonomous drone behavior via MCDM of UFOMap layers

2024-04-19 · 1 citations