Whole‐exome sequencing reveals novel <i>USP9X</i> variant in female fetus with isolated agenesis of the corpus callosum

Lenberg, Jerica; Pretorius, Dolores H.; Rupe, Eric S.; Jones, Marilyn C.; Ramos, Gladys A.; Andreasen, Tara S.

doi:10.1002/ccr3.2051

Cited by 2 publications

(3 citation statements)

References 17 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fetuses with apparently isolated CCA, the rate of significant pathological copy number variations and normal karyotype has been reported to be 5.7% [11]. A recent joint committee opinion of the American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) recommended that CMA analysis should be performed in all fetuses undergoing invasive procedures for major structural anomalies detected on US [11,[14][15][16]. Nevertheless, these techniques cannot detect discrete gene mutations involved in various monogenic disorders [11,15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Advances in new genetic diagnostic techniques, such as next-generation sequencing, whole-genome sequencing (WGS), and particularly whole-exome sequencing (WES) [14][15][16][17], may help determine the underlying cause of CCA especially in those cases not presenting with the classical clinical features of a syndromic condition [14][15][16] and in fetuses with normal karyotype and CMA. WGS analyzes the entire genome.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review

Cunha

Carneiro

Miguel³

et al. 2021

Fetal Diagn Ther

View full text Add to dashboard Cite

Abnormalities of corpus callosum are one of the most common brain anomalies. Fetuses with isolated corpus callosum agenesis (CCA) have a better prognosis than those with additional anomalies. However, unpredictable neurodevelopmental outcomes of truly isolated CCA make prenatal counseling a challenge. The aim of this review is to evaluate neurodevelopmental outcomes in children with prenatal diagnosis of isolated CCA. Controlled clinical trials published between May 23, 2009, and May 23, 2019, using the MeSH term “agenesis of corpus callosum” were reviewed. A total of 942 articles were identified, and 8 studies were included in the systematic review depending on the inclusion criteria. These studies included 217 fetuses with isolated CCA and no other anomalies at prenatal assessment. Neurodevelopmental outcome was reported to be normal in 83 children with a prenatal diagnosis of isolated CCA confirmed at birth within 128 completed assessments. About 45 children presented borderline, moderate, or severe neurodevelopmental outcome. In this review, neurodevelopment was favorable in two-thirds of the cases, but mild disabilities emerged in older children. Despite this, disabilities can occur later beyond school age and a low risk of severe cognitive impairment exists. Our study highlights the essential early diagnosis and proper supportive therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review

Cunha

Carneiro

Miguel³

et al. 2021

Fetal Diagn Ther

View full text Add to dashboard Cite

show abstract

“…Molecularly, this cohort was reported with nonsense, frameshift, missense variants, and intragenic and inframe germline deletions in USP9X ( Figure 2 A). 4 , 5 , 27 , 28 , 29 , 30 , 31 , 32 , 33 The clinical importance of exon 33 (deleted in the GOBACK proband) is implicated by the overlap of this exon with 2 pathogenic missense variants p.D1685N and p.L1693W, previously reported in 3 female patients: Jolly et al females 26, 27, and Jolly et al. female 8 with this disorder 4 , 5 ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 80%

Identification of USP9X as a leukemia susceptibility gene

Sisoudiya

Mishra

et al. 2023

Blood Advances

View full text Add to dashboard Cite

We recently reported that children with multiple birth defects have a significantly higher risk of childhood cancer. We performed whole genome sequencing on a cohort of probands from this study with birth defects and cancer and their parents. Structural variant analysis identified a novel 5kb de novo heterozygous in-frame deletion overlapping the catalytic domain of USP9X in a female proband with multiple birth defects, developmental delay and B-cell acute lymphoblastic leukemia (B-ALL). Her phenotype was consistent with female-restricted X-linked syndromic intellectual developmental disorder-99 (MRXS99F). Genotype-phenotype analysis including previously reported female probands (n=42) demonstrated that MRXS99F probands with B-ALL (n=3) clustered with subjects with loss-of-function (LoF) USP9X variants and multiple anomalies. The cumulative incidence of B-ALL among these female probands (7.1%) was significantly higher than an age- and sex-matched cohort (0.003%) from the Surveillance, Epidemiology, and End Results (SEER) database (P<0.0001, log-rank test). There are no reports of LoF variants in males. Males with hypomorphic missense variants have neurodevelopmental disorders without birth defects or leukemia risk. Conversely, in sporadic B-ALL, somatic LoF USP9X mutations occur in both males and females and expression levels are comparable in leukemia samples from both sexes (P=0.54) with the highest expressors being female patients with extra copies of X-chromosome. Overall, we describe USP9X as a novel female-specific leukemia predisposition gene associated with multiple congenital, neurodevelopmental anomalies, and B-ALL risk. In contrast, USP9X serves as a tumor suppressor in sporadic pediatric B-ALL in both sexes with low expression associated with poorer survival in high-risk B-ALL patients.

show abstract

Whole‐exome sequencing reveals novel USP9X variant in female fetus with isolated agenesis of the corpus callosum

Cited by 2 publications

References 17 publications

Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review

Neurodevelopmental Outcomes following Prenatal Diagnosis of Isolated Corpus Callosum Agenesis: A Systematic Review

Identification of USP9X as a leukemia susceptibility gene

Contact Info

Product

Resources

About