Central 22q11.2 deletion (<scp>LCR22 B‐D</scp>) in a fetus with severe fetal growth restriction and a mother with severe systemic lupus erythematosus: Further evidence of <scp><i>CRKL</i></scp> haploinsufficiency in the pathogenesis of 22q11.2 deletion syndrome

Lin, Isabella; Afshar, Yalda; Goldstein, Jeffrey; Grossman, Jennifer M.; Grody, Wayne W.; Quintero‐Rivera, Fabiola

doi:10.1002/ajmg.a.62346

Cited by 6 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 22q11.2DS is usually diagnosed by FISH using commercial probes, including TUPLE1 (flanked by LCR A-B of 22q11.2 deletion). Another limitation of the study is that this probe has a detection yield of 85% for classic 2.55 Mb deletion spanning LCR A-D but only 5% and 2% of the atypical deletions spanning LCR A-B and A-C, respectively 4,13,14,16 . Therefore, it is possible that our interphase FISH studies missed some cases with deletions without the involvement of the A-B region.…”

Section: Discussionmentioning

confidence: 99%

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico

Fabián-Morales¹,

Bobadilla-Morales²,

Peña-Padilla³

et al. 2022

BMHIM

View full text Add to dashboard Cite

Background: Congenital heart defects (CHD) are among the most frequent manifestations of 22q11.2 deletion syndrome. Although we found relatively few studies aimed at specifically detecting 22q11.2 deletion in newborns (NB) with CHD, none of them has been performed in Mexico. Methods: We conducted a prospective hospital-based study from January 2017 to March 2021 in the Genetics and Pediatric Cardiology Services of the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). All consecutive NBs identified with any non-syndromic major CHD confirmed by echocardiography were eligible to participate. A total of 98 NBs were included, 51 males and 47 females. Fluorescence in situ hybridization (FISH) analysis was conducted to search for deletion of chromosome 22q11.2 in interphase nuclei of standard lymphocyte cultures. Results: We found eight patients (8.2%) with CHD and the 22q11.2 deletion, all of them with conotruncal defects, particularly of the truncus arteriosus (p = 0.013), tetralogy of Fallot (p = 0.024), and pulmonary atresia with ventricular septal defect (p = 0.031) subtypes. With de exception of one infant with hypocalcemia and another with hypocalcemia and thymic aplasia, the diagnosis of 22q11.2 deletion was not clinically suspected in the other patients. Conclusions: Our results confirm the importance of excluding the presence of the 22q11.2 deletion in every NB with CHDs, particularly of the conotruncal subtype, even in the absence of other manifestations.

show abstract

Section: Discussionmentioning

confidence: 99%

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico

Fabián-Morales¹,

Bobadilla-Morales²,

Peña-Padilla³

et al. 2022

BMHIM

View full text Add to dashboard Cite

show abstract

“…Among them, 15q24 Microdeletion Syndrome (#613,406) and 8q21.11 Microdeletion Syndrome (#614,230) were rarely characterized by FGR 25 . As for 22q11.21 microdeletion, which is responsible for DiGeorge Syndrome or Velocardiofacial Syndrome, FGR was frequently reported in FGR with structural malformations 12 , 26 – 28 . In one case (case 1) presenting FGR and ventricular septal defect (VSD), a 2.6 Mb deletion was detected in the region of 3q26.33-3q27.2, involving 30 OMIM genes.…”

Section: Discussionmentioning

confidence: 99%

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations

Wu,

He,

Shen

et al. 2024

Sci Rep

View full text Add to dashboard Cite

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

show abstract

“…When neurons are edema, degeneration, and necrosis, NSE can be released into cerebrospinal fluid and blood. Many scholars have confirmed that the level of serum NSE is significantly increased in cerebrovascular disease, neonatal hypoxic-ischemic encephalopathy, epilepsy, cardiogenic hypoxic-ischemic brain injury, brain trauma, and other diseases [ 26 ]. Among the data of our study, one patient with SLE had no neuropsychiatric symptoms and signs on admission, but his serum NSE increased significantly, and she had a major seizure 2 days later.…”

Section: Discussionmentioning

confidence: 99%

“…However, because of its hidden performance and no specific and sensitive diagnostic methods, it is often ignored in clinical work, so it cannot be treated timely. The change of serum NSE level can early and specifically reflect the pathological changes of CNS during SLE, so it may be employed as a sensitive index to judge the existence of lupus encephalopathy in the early stage so as to provide a theoretical basis for the prevention and treatment of lupus encephalopathy [ 26 ]. At present, the detailed mechanism of the increase of serum NSE in SLE is not well understood, but it is believed to be mainly related to the following: (1) a variety of autoantibodies (antinuclear antibodies and anti-brain cell antibodies) combine with corresponding antigens to form immune complexes with the complements, which deposit on the blood vessel wall to cause cerebral vasculitis; (2) some small emboli form heart valve vegetations; (3) anticardiolipin antibodies directly act on the phospholipid components of vascular endothelial cells and platelets, leading to small thrombosis, causing microinfarction, hemorrhage, edema and brain tissue softening, and other factors, which lead to CNS lesions in patients with SLE, resulting in the increase of serum NSE levels, but the course and prognosis of NSE and SLE need to be further studied [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of Serum Neuron‐Specific Enolase Combined with Serum S100B Protein in the Diagnosis of Systemic Lupus Erythematosus

Chen

Cheng²,

Zhang

et al. 2022

Contrast Media & Molecular Imaging

View full text Add to dashboard Cite

Objective. To investigate the clinical value of serum neuron-specific enolase (NSE) combined with serum S100B protein in the diagnosis of systemic lupus erythematosus (SLE). Methods. Sixty patients with SLE treated in our hospital from January 2019 to April 2021 were enrolled as the study group. According to the degree of activity, the study group was assigned into three groups: mild activity group (n = 20), moderate activity group (n = 20), and severe activity group (n = 20). A total of 60 healthy people who underwent physical examination in our hospital in the same period were enrolled as the control group. The NSE and serum S100B protein were detected in the two groups, and the correlation between serum nerve-specific enolase and serum S100B protein and the clinical value in the diagnosis of SLE were analyzed. Results. First of all, we compared the general data of the two groups. There was no significant difference in sex, age, marital status, and education level, and no significant difference was exhibited ( p > 0.05). There was no significant difference in sex, age, marital status, and education level among mild activity group, moderate activity group, and severe activity group, and no significant difference in data was exhibited ( p > 0.05). Secondly, we compared the levels of serum S100B protein and NSE. The levels of serum S100B protein and NSE in the study group were higher compared to the control group ( p < 0.05). The levels of serum S100B protein and NSE in patients with different activity levels of SLE were compared. The levels of serum S100B protein and NSE in mild activity group < moderate activity group < severe activity group were significantly different ( p < 0.05). Correlation analysis between serum S100B, NSE levels, and SLE activity indicated that serum S100B and NSE levels were positively correlated with SLE activity. With the increase of SLE activity, serum S100B and NSE levels gradually increased, and the data difference was statistically significant (r = 0.855, 0.844, p < 0.05). Finally, we established the logistic prediction model, take the probability of generating prediction as the analysis index, and draw the ROC curve to evaluate the diagnostic value of different combinations to SLE. The highest AUC and sensitivity of the two indexes in the diagnosis of SLE were 0.773 and 0.836, respectively. The levels of serum S100B protein and NSE have a certain value in the diagnosis of SLE, while the combined diagnosis is of higher value, sensitivity, and specificity in the diagnosis of SLE. Conclusion. Serum S100B protein and NSE are very sensitive indexes to judge the damage of central nervous system. However, due to the small number of cases in this study, there were as many as 19 kinds of NPSLE classification, so the relationship between serum S100B protein, NSE levels, and various NPSLE and their exact application value in diagnosing the disease and judging the prognosis needs to be confirmed by expanding the number of cases.

show abstract

Central 22q11.2 deletion (LCR22 B‐D) in a fetus with severe fetal growth restriction and a mother with severe systemic lupus erythematosus: Further evidence of CRKL haploinsufficiency in the pathogenesis of 22q11.2 deletion syndrome

Cited by 6 publications

References 22 publications

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations

Clinical Value of Serum Neuron‐Specific Enolase Combined with Serum S100B Protein in the Diagnosis of Systemic Lupus Erythematosus

Contact Info

Product

Resources

About