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Autosomal Recurrent Primary Microscopic (MCPH, OMIM: 251200) is a neurodevelopmental disorder that is characterized by a noticeable decrease in brain size, particularly in the cerebral cortex, but with a normal brain structure and a non-progressive intellectual disability. MCPH1 has been identified as the gene that triggers primary microcephaly (MCPH1，OMIM: 607117). Here we report a case of autosomal recessive primary microcephaly as caused by a novel variant in the MCPH1 gene. Head circumference was measured by Magnetic Resonance Imaging (MRI), while the Wechsler Intelligence Scale was used to evaluate the intelligence of the individual being tested. B-ultrasound was used to assess gonadal development, and semen routine was used to assess sperm status. The whole-exome sequencing (WES) was performed on the proband. Sanger sequencing was conducted on the parents of the proband to determine if the novel variant in the MCPH1 gene was present. The effect of the mutation on the splicing of MCPH1 was verified by minigene approach. It was observed that the proband had autosomal recessive primary microcephaly and azoospermatism. A novel splice-site homozygous mutation (c.233+2T > G) of the MCPH1 gene was identified, which inherited from his parents. Minigene approach confirmed that c.233+2T > G could affect the splicing of MCPH1. Therefore, our findings contributed to the mutation spectrum of the MCPH1 gene and may be useful in the diagnosis and gene therapy of MCPH.

Background: The most common disease caused by biallelic AFG3L2 mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic AFG3L2 mutations has been increasing in recent years. Methods: A retrospective analysis was performed on a child with microcephaly and recurrent seizures. The child underwent physical and neurological examinations, laboratory tests, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Trio-whole-exome sequencing (trio-WES) was performed to identify possible causative mutations. Results: We described a child who exhibited early-onset and intractable epilepsy, developmental regression, microcephaly, and premature death. Neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum, corpus callosum, brainstem, cerebellar vermis, and basal ganglia. On trio-WES, two novel compound heterozygous mutations, c.1834G > T (p.E612*) and c.2176-6T > A in the AFG3L2 gene, were identified in this patient. Conclusions: Our findings have expanded the mutation spectrum of the AFG3L2 gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.

Objective: The aim of this study was to gain a better understanding of the molecular mechanisms and identify more critical genes associated with the pathogenesis of postmenopausal osteoporosis (PMOP). Materials and Methods: Microarray data of GSE13850 were download from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified either in B cells from postmenopausal female nonsmokers with high bone mineral density (BMD) compared with those with low BMD (defined as DEG1 group) or in B cells from postmenopausal female smokers with high BMD compared with postmenopausal female nonsmokers with high BMD (defined as DEG2 group). Gene ontology and immune-related functional enrichment analysis of DEGs were performed. Additionally, the protein–protein interaction network of all DEGs was constructed and subnetworks of the hub genes were extracted. Results: A total of 51 DEGs were identified in the DEG1 group, including 30 up- and 21 downregulated genes. Besides, 86 DEGs were identified in the DEG2 group, of which 46 were upregulated and 40 were downregulated. Immune enrichment analysis showed DEGs were mainly enriched in functions of CD molecules and chemokines and receptor, and the upregulated gene interleukin 4 receptor (IL-4R) was significantly enriched. Moreover, guanine nucleotide-binding protein G (GNAI2), filamin A alpha (FLNA), and transforming growth factor-β1 (TGFB1) were hub proteins in the protein–protein interaction network. Conclusion: IL-4R, GNAI2, FLNA, and TGFB1 may be potential target genes associated with the pathogenesis of PMOP. In particular, FLNA, and TGFB1 may be affected by smoking, a risk factor of PMOP.