Dataset Information

Congenital dyserythropoiesis anemia type Ia with a novel CDAN1 mutation diagnosed by whole exome sequencing.

ABSTRACT:

Background

Congenital dyserythropoiesis anemia type Ia (OMIM:224120), is a rare hereditary anemia. The diagnosis is difficult to make and usually delayed in part due to its rarity and nonspecific clinical manifestations.

Methods

Whole exome sequencing was applied for the genetic diagnosis of a 12-year-old boy who has suffered from hemolytic anemia since birth and who requires regular transfusions. Sanger sequencing of the variants detected in whole exome sequencing was performed in the patient and his parents.

Results

Compound heterozygous mutations of CDAN1 gene, including one previously reported and one novel mutation, which is a splicing change, were detected in the whole exome sequencing and confirmed by Sanger sequencing. The autosomal recessive inheritance was confirmed by pedigree analysis.

Conclusion

To our knowledge, this is the first case report of congenital dyserythropoiesis anemia type Ia with genetic diagnosis to be located in Taiwan. Because of the rarity of CDA Ia and the overlapping of the clinical manifestations with other hereditary anemias, the next-generation sequencing approach is effective for conclusive diagnosis of CDA Ia.

SUBMITTER: Lin PC

PROVIDER: S-EPMC7216794 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Congenital dyserythropoiesis anemia type Ia with a novel CDAN1 mutation diagnosed by whole exome sequencing.

Lin Pei-Chin PC Cheng Chao-Neng CN Huang Hsi-Yuan HY Tseng Yu-Hsin YH Chang Ya-Sian YS Lin Chien-Yu CY Chang Jan-Gowth JG

Molecular genetics & genomic medicine 20200311 5

<h4>Background</h4>Congenital dyserythropoiesis anemia type Ia (OMIM:224120), is a rare hereditary anemia. The diagnosis is difficult to make and usually delayed in part due to its rarity and nonspecific clinical manifestations.<h4>Methods</h4>Whole exome sequencing was applied for the genetic diagnosis of a 12-year-old boy who has suffered from hemolytic anemia since birth and who requires regular transfusions. Sanger sequencing of the variants detected in whole exome sequencing was performed i ...[more]

PMID: 32160409

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Project description:Context: Congenital hypothyroidism due to thyroid dysgenesis (CHTD) is a predominantly sporadic and nonsyndromic (NS) condition of unknown etiology. NS-CHTD shows a 40-fold increase in relative risk among first-degree relatives (1 in 100 compared with a birth prevalence of 1 in 4000 in the general population), but a discordance rate between monozygotic (MZ) twins of 92%. This suggests a two-hit mechanism, combining a genetic predisposition (incomplete penetrance of inherited variants) with postzygotic events (accounting for MZ twin discordance). Objective: To evaluate whether whole-exome sequencing (WES) allows to identify new predisposing genes in NS-CHTD. Methods: We performed a case-control study by comparing the whole exome of 36 nonconsanguineous cases of NS-CHTD (33 with lingual thyroid ectopy and 3 with athyreosis, based on technetium pertechnetate scintigraphy at diagnosis) with that of 301 unaffected controls to assess for enrichment in rare protein-altering variants. We performed an unbiased approach using a gene-based burden with a false discovery rate correction. Moreover, we identified all rare pathogenic and likely pathogenic variants, based on in silico prediction tools, in 27 genes previously associated with congenital hypothyroidism (CH) (thyroid dysgenesis [TD] and dyshormonogenesis). Results: After correction for multiple testing, no enrichment in rare protein-altering variants was observed in NS-CHTD. Pathogenic or likely pathogenic variants (21 variants in 12 CH genes) were identified in 42% of cases. Eight percent of cases had variants in more than one gene (oligogenic group); these were not more severely affected than monogenic cases. Moreover, cases with protein-altering variants in dyshormonogenesis-related genes were not more severely affected than those without. Conclusions: No new predisposing genes were identified following an unbiased analysis of WES data in a well-characterized NS-CHTD cohort. Nonetheless, the discovery rate of rare pathogenic or likely pathogenic variants was 42%. Eight percent of the cases harbored multiple variants in genes associated with TD or dyshormonogenesis, but these variants did not explain the variability of hypothyroidism observed in dysgenesis. WES did not identify a genetic cause in NS-CHTD cases, confirming the complex etiology of this disease. Additional studies in larger cohorts and/or novel discovery approaches are required.

Dataset Information

Congenital dyserythropoiesis anemia type Ia with a novel CDAN1 mutation diagnosed by whole exome sequencing.

Background

Methods

Results

Conclusion

Publications

Congenital dyserythropoiesis anemia type Ia with a novel CDAN1 mutation diagnosed by whole exome sequencing.

Similar Datasets

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