A rare inherited homozygous missense variant in PLA2G6 influences susceptibility to infantile neuroaxonal dystrophy: a case report.

Background: Infantile neuroaxonal dystrophy (INAD) is an ultra-rare early-onset autosomal recessive neurodegenerative disorder due to PLA2G6 variants. The clinical symptoms of INAD patients display considerable diversity, and many PLA2G6 variants are still not thoroughly investigated in relation to their associated clinical presentations. Case Description: A 16-month-old boy was admitted to our hospital due to regression of acquired motor and speech abilities that had persisted for 4 months. The patient was born to a healthy consanguineous couple after 41 weeks of pregnancy and natural delivery. Before 12 months old, he had normal motor development milestones. On admission, he also showed astasia-abasia, weakness of distal muscles, and diminished patellar tendon reflex. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy. Auditory brainstem response (ABR) indicated moderately severe hearing loss. With chromosome microarray analysis (CMA), we identified several copy number-neutral regions of runs of homozygosity (ROH) in the patient. Whole-exome sequencing (WES) further revealed that the patient harbored a homozygous missense variant NM_003560.2: c.1778C>T, p.Pro593Leu (rs1451486649) in the PLA2G6 gene. In the patient's asymptomatic parents and brother, the PLA2G6 c.1778C>T variant stayed in heterozygous status as confirmed by Sanger sequencing. The patient was finally diagnosed with INAD. Conclusions: We report an INAD child with a rare PLA2G6 c.1778C>T homozygous missense variant and associated clinical symptoms. The family-based cosegregation analysis reveals that the PLA2G6 c.1778C>T homozygous variant contributes to the pathogenesis of INAD.

[Clinical phenotype and genetic analysis of a child featuring short stature and multiple skeletal dysplasia].

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child featuring familial short stature. METHODS: A child who was admitted to Huzhou Maternal and Child Health Care Hospital on October 7, 2021 for growth retardation and pectus carinatum was selected as the study subject. Physical exam and medical imaging was performed. The child was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 1-year-old male, had manifested with slightly short stature (Z = -2.03), midfacial dysplasia, and multiple skeletal dysplasia such as pectus carinatum, irregular vertebral morphology, and defect of lumbar anterior bones. His mother, maternal grandmother and great-maternal grandfather also had short stature. WES revealed that the child has harbored a heterozygous c.2858dupA (p.Asp953GlufsTer476) frameshifting variant of the ACAN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2858dup (p.Sp953Glufster476) variant was classified as likely pathogenic (PVS1+PM2_Supporting). The patient has shown marked improved height after receiving 11 months of treatment with human recombinant growth hormone (supplemental dose) starting from 20 months of age. CONCLUSION: The ACAN: c.2858dup (p.Asp953GlufsTer476) variant probably underlay the pathogenesis of short stature in this child.

[Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. METHODS: A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. RESULTS: Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. CONCLUSION: The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

[Prediction and analysis of B cell and T cell epitopes in the spike protein of SARS-CoV-2 by bioinformatics].

Objective To analyze structural features for spike (S) protein of the SARS-CoV-2 and to predict potential B cell and T cell epitopes using bioinformatics. Methods The amino acid sequence of S protein from the NCBI GenBank database was retrieved. Its physicochemical properties were analyzed using ProtParam online program. The secondary structure of S protein was analyzed using Lasergene software and SOPMA online service. The tertiary structure model of S protein was established by Phyre2 and Rasmol software. Finally, B cell epitopes were predicted using ABCpred, BepiPred and BcePred; T cell epitopes were predicted using IDBE software. Results S protein is a 1273 amino acid sequence with the isoelectric point at 6.24 and atomic composition as C6336H9770N1656O1894S54, which was classified as a stable and hydrophilic protein. GramierRobson method analysis revealed that the secondary structure of S protein comprised 23.5% α-helixes, 53.7% ß-sheets, 14.9% ß-turns and 8.33% random coils. Chou-Fasman method analysis revealed that the secondary structure of S protein comprised 20.9% α-helixes, 35.5% ß-sheets, 35.2% ß-turns. Online service SOPMA analysis revealed that the secondary structure of S protein comprised 28.59% α-helixes, 23.25% ß-sheets, 3.38% ß-turns and 44.78% random coils. The numbers of B cell epitopes according to ABCpred, BepiPred and BcePred databases were 5,11 and 6. Five epitopes for CD8+ T cell and CD4+ T cell were chosen as potential epitopes. Conclusion Bioinformatics can predict B cell and T cell epitopes in the S protein of the SARS-CoV-2, which lays a foundation for developing vaccines.