Identification of the first Alu-mediated gross deletion involving the BCKDHA gene in a compound heterozygous patient with maple syrup urine disease

Ma, Shujun; Zhang, Zhongxin; Fu, Ying-Shuang; Zhang, Mingxia; Niu, Yuna; Li, Ruiguang; Guo, Qisen; He, Zhi-An; Zhao, Qian; Song, Zhishan; Wang, Xia; Sun, Ruili

doi:10.1016/j.cca.2021.01.023

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Further haplotypic analysis is warranted to support the latter hypothesis. Regarding the potential impact of methodologic issues, we note that the short-read WGS strategy is generally intended to approximately localize the breakpoints of a gross genomic structural rearrangement (e.g., a deletiontype CNV); to reach the nucleotide level of resolution, it could be necessary to apply long-range PCR and Sanger sequencing [26,27], as performed herein. Given this, we propose that it would be desirable to determine the precise nucleotide-level rearrangements of the esv3587290 CNV in other populations.…”

Section: Discussionmentioning

confidence: 99%

Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?

ALCÁNTARA-ORTIGOZA,

Rodríguez-Lozano,

Estandía-Ortega

et al. 2024

Preprint

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A ~3-kb deletion-type DNA copy-number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor for developing lupus nephritis (LN) in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N=37) or without (N=29) LN, as diagnosed by renal biopsy (N=15), proteinuria (N=33), urinary protein:creatinine ratio >0.2 (N=34), and erythrocyturia and/or granular casts in urinary sediment (N=16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation by Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically-matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium (HWE) by 2 test. Associations between LN and esv3587290 CNV were tested by calculating the Odds Ratio (OR) and using Pearson's 2 tests with a 95% confidence interval and p≤0.05. Contrary to the results described in European-descent populations, the esv3587290 CNV showed a significant protective effect against LN development (OR 0.14, 95% CI 0.066-0.31, p≤0.05), whereas the wild-type homozygous VANGL1 genotype showed a risk trend for LN development (OR 2.15, 95% CI 0.7711-6.18, p≤0.05). Finally, we characterized the precise breakpoint of the esv3587290 CNV as NG_016548.1(NM_138959.3):c.1314+1339_1315-897del (https://databases.lovd.nl/shared/variants/0000918418#00025811) in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.

show abstract

Section: Discussionmentioning

confidence: 99%

Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?

ALCÁNTARA-ORTIGOZA,

Rodríguez-Lozano,

Estandía-Ortega

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Further haplotypic analysis is warranted to support the latter hypothesis. Regarding the potential impact of methodologic issues, we note that the short-read WGS strategy is generally intended to approximately localize the breakpoints of a gross genomic structural rearrangement (e.g., a deletion-type CNV); to reach a nucleotide-level resolution, it would be necessary to apply long-range PCR and Sanger sequencing [ 26 , 27 ], as performed herein. Given this, we propose that it would be desirable to determine the precise nucleotide-level rearrangements of the esv3587290 CNV in other populations.…”

Section: Discussionmentioning

confidence: 99%

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

Alcántara-Ortigoza,

Rodríguez-Lozano,

Estandía-Ortega

et al. 2024

Children

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A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein–creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy–Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson’s χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034–0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119–0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.

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Long-range and real-time PCR identification of a large SERPINC1 deletion in a patient with antithrombin deficiency

Matsumoto,

Uchiumi,

Ueyanagi

et al. 2024

Int J Hematol

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Identification of the first Alu-mediated gross deletion involving the BCKDHA gene in a compound heterozygous patient with maple syrup urine disease

Cited by 3 publications

References 30 publications

Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?

Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

Long-range and real-time PCR identification of a large SERPINC1 deletion in a patient with antithrombin deficiency

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