Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities (MIM # 618092) is a congenital disorder derived from pathogenic variants of the B-cell leukemia/lymphoma 11B gene (BCL11B). Several variants have been reported to date. Here, through comprehensive genomic analysis, a novel BCL11B truncation variant, NM_138576.4(BCL11B_v001): c.2439_2452dup [p.(His818Argfs*31)], was identified in a Japanese male patient with developmental delay, distinctive features, and early craniosynostosis.
chromosomal microarray testing, 6q interstitial deletions, developmental delay Interstitial microdeletions in the proximal region of the long arm of chromosome 6 are rare. Herein we have reported 12 patients with developmental delays associated with interstitial microdeletions in 6q ranging from q12 to q22. The microdeletions were detected by chromosomal microarray testing. To confirm the clinical significance of these deletions, genotype-phenotype correlation analysis was performed using genetic and predicted loss-of-function data. SIM1 was recognized as the gene responsible for developmental delay, particularly in Prader-Willi syndrome-like phenotypes. Other genes possibly related to developmental delay were ZNF292, PHIP, KCNQ5, and NUS1. To further establish the correlation between the genotype and phenotype, more patient information is required.
The guidelines provided by American College of Medical Genetics and Genomics (ACMG) and the Association of Molecular Pathology (AMP) (ACMG/AMP guidelines) suggest a framework for the classification of clinical variants. However, the interpretations can be inconsistent, with each definition sometimes proving to be ambiguous. In particular, there can be difficulty with interpretation of variants related to the X-linked recessive trait. To confirm whether there are biases in the interpretation of inherited traits, we reanalyzed variants reported prior to the release of the ACMG/AMP guidelines. As expected, the interpretation ratio as pathogenic or likely pathogenic was significantly lower for variants related to the X-linked recessive trait. Evaluation of variants related to the X-linked recessive trait, hence, need to consider whether the variant is identified only in males in accordance with the X-linked recessive trait. The ACMG/AMP guidelines should be revised to eliminate the bias revealed in this study.
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