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Background: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat‐containing adaptor 6B protein. Methods: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole‐exome sequencing and Sanger sequencing. Results: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café‐au‐lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. Conclusion: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome. [ABSTRACT FROM AUTHOR]

Nitrogen permease regulator‐like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3‐related epilepsy is a range of epilepsy‐associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep‐related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3‐related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C > T, p.Gln392*) and a missense variant (c.1322C > T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3‐related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the existence ofNPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3‐related epilepsy. Plain Language Summary: This study expands the phenotypic and genotypic spectra of NPRL3‐related epilepsy by reporting two cases with different novel variants. Following a review of the literature, it was observed that patients harboring various NPRL3 variants exhibited a variability of clinical manifestations. Also, patients carrying nonsense mutations are frequently prone to drug resistance and other severe comorbidities such as developmental delay, but more cases need to be collected to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Mega‐corpus‐callosum syndrome with cerebellar hypoplasia and cortical malformations is a rare neurological disorder that is associated with typical clinical and imaging features. The syndrome is caused by pathogenic variants in the MAST1 gene, which encodes a microtubule‐associated protein that is predominantly expressed in postmitotic neurons in the developing nervous system. Methods: Fetal DNA from umbilical cord blood samples and genomic DNA from peripheral blood lymphocytes were subjected to whole‐exome sequencing. The potential causative variants were verified by Sanger sequencing. Results: A 26‐year‐old primigravid woman was referred to our prenatal center at 25 weeks of gestation due to abnormal ultrasound findings in the brain of the fetus. The brain abnormalities included wide cavum septum pellucidum, shallow and incomplete bilateral lateral fissure cistern, bilateral dilated lateral ventricles, hyperplastic corpus callosum, lissencephaly, and cortical dysplasia. No obvious abnormalities were observed in the brainstem or cerebellum hemispheres, but the cerebellum vermis was small. Whole‐exome sequencing identified a de novo, heterozygous missense variant, c.695T>C(p.Leu232Pro), in the MAST1 gene and a genetic diagnosis of mega‐corpus‐callosum syndrome was considered. Conclusion: This study is the first prenatal case of MAST1‐related disorder reported in the Chinese population and has expanded the mutation spectrum of the MAST1 gene. [ABSTRACT FROM AUTHOR]