Novel BCL11B truncation variant in a patient with developmental delay, distinctive features, and early craniosynostosis

Abstract

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.

Fig. 1. Clinical information of the patient.

Facial appearance of the patient at 6 months of age (a, b) and 5 years of age (c, d), suggesting deformity of the skull, forehead protrusion, arched eyebrows, flat nose base, thin upper lip, small mouth, long philtrum, retrognathia and low-set ears. e 3-dimensional CT image of the skull at 10 months of age shows partial early fusion of the sagittal and lambda sutures (arrows). T1-(f) and T2-(g)-weighted brain MRI at 11 months of age showed no apparent abnormalities.

Fig. 2. Results of genetic analysis.

a Sanger sequencing indicates overlapping electropherograms due to the 14-bp duplication. b Locations of the BCL11B variants are depicted on the primary structure (modified data from Prasad et al., 2020). The positions of the previously reported BCL11B variants are shown in black. The variant reported in this study is shown in red (in the 4th zinc-finger motif). Most of the variants are located on exon 4. Circles, rhombuses, triangles, and rectangles indicate missense, truncation, nonsense, and splicing mutations, respectively. NH3 N-terminus, COOH C-terminus.