The homozygous loss-of-function variant of BICD2 is associated with cerebral hypoplasia and cerebral hypoplasia

The specified variable p. (Gln77Ter) is new and absent from the genome assembly database. It has been shown that pathogenic variants in BICD2 Extremely rare in the population, expected to be harmful by most tools, and occur at specific hotspots within the switch BICD2 Functional areas [8]. Furthermore, WES did not identify any variant(s) in any of the OMIM genes with a recognized disease association (including VPS13B gene). despite BICD2 Necessary for the proper development of the cerebral cortex [5] But there have been no other clinical reports of individuals with loss-of-function variants in BICD2 Show cerebral hyperplasia and cerebellar hypoplasia. However, lissencephaly and cerebellar hypoplasia are in agreement with that observed after BICD2 knockdown in mice showing defects in the laminar organization of the cerebral cortex, hippocampus and cerebellar cortex, indicative of defects in radial neuronal migration. Cell-specific inactivation of BICD2 in astrocytes and neuronal precursors revealed that migration of radial cerebellar granule cells is non-autonomous and intrinsic to Bergmann cerebellar glia cells. [9, 10]. So we looked BICD2 To be a convincing candidate gene in the context of encephalitis and cerebellar hypoplasia. No homozygous loss of function BICD2 Variants in healthy family members support the clinical significance of BICD2.

More recently, the biallelic variant c.731 T>C p. (Leu244Pro) in BICD2 Described in a girl with an abnormal gyral pattern in the frontal and parietal regions [6] (Table 1). The girl also showed moderate intellectual disability and Cohen-like features [6]. In contrast, our patient showed congenital microcephaly, severe retardation, seizures, and brain hypoplasia. In contrast to the patient with Cohen-like traits, our patient showed spasticity and contractile abnormalities and did not show neutropenia. Interestingly, a heterozygous missense variant c.2080 C>T, p. (Arg694Cys) in two unrelated patients with mild innate polymorphism, and moderate cerebellar hypoplasia. [4]. Moreover, a BICD2 The absurd variation of p. (Lys775Ter) in a boy with cerebral and subcortical asymmetry. [5]. These heterozygous variants are located within the highly conserved CC3 domain of BICD2 (Table 1). However, heterogeneous missense variants within the CC1 domain were not associated with abnormalities in cortical development, but also showed a milder SMALED2A pathway and a higher frequency of foot abnormalities. [8]. Indeed, a larger group is needed to draw conclusions regarding genotype-phenotype associations.

Table 1 Clinical outcomes and variables identified in patients with BICD2 and cerebral anomalies

The cerebral hypertrophy and cerebellar hypoplasia observed in our patient appeared similar to those with LIS1 variables. This is not surprising LIS1 It interacts with the dynein/dynactin complex and BICD2 to recruit cellular structures [11]. In the meantime, MRI features of the brain may interfere realnPhenotype of rash-lowering patients. However, the cortical migration defect was more severe in our patient than in realnPatients subject to rash. In addition, our patient had mild hypoplasia in contrast to the cerebellum realnPatients subject to rash and who have a hyperplastic and dysplastic cerebellum with no identifiable folliculitis [12].

Our study provides valuable findings in disorders of human developmental brain abnormalities associated with final loss-of-function variants in BICD2.