Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.

BACKGROUND: Auriculocondylar syndrome (ARCND) is a rare congenital craniofacial developmental malformation syndrome of the first and second pharyngeal arches with external ear malformation at the junction between the lobe and helix, micromaxillary malformation, and mandibular condylar hypoplasia. Four subtypes of ARCND have been described so far, that is, ARCND1 (OMIM # 602483), ARCND2 (ARCND2A, OMIM # 614669; ARCND2B, OMIM # 620458), ARCND3 (OMIM # 615706), and ARCND4 (OMIM # 620457). METHODS: This study reports a case of ARCND2 resulting from a novel pathogenic variant in the PLCB4 gene, and summarizes PLCB4 gene mutation sites and phenotypes of ARCND2. RESULTS: The proband, a 5-day-old male neonate, was referred to our hospital for respiratory distress. Micrognathia, microstomia, distinctive question mark ears, as well as mandibular condyle hypoplasia were identified. Trio-based whole-exome sequencing identified a novel missense variant of NM_001377142.1:c.1928C>T (NP_001364071.1:p.Ser643Phe) in the PLCB4 gene, which was predicted to impair the local structural stability with a result that the protein function might be affected. From a review of the literature, only 36 patients with PLCB4 gene mutations were retrieved. CONCLUSION: As with other studies examining familial cases of ARCND2, incomplete penetrance and variable expressivity were observed within different families' heterozygous mutations in PLCB4 gene. Although, motor and intellectual development are in the normal range in the vast majority of patients with ARCND2, long-term follow-up and assessment are still required.

Clinical report and genetic analysis of a Chinese neonate with craniofacial microsomia caused by a splicing variant of the splicing factor 3b subunit 2 gene.

BACKGROUND: Craniofacial microsomia (CFM) is a common congenital malformation with unknown pathogenesis. Although few cases have been reported, it is suggested that variants of the SF3B2 gene may lead to CFM. We herein report the case of a neonate with CFM exhibiting rare features of airway obstruction. METHODS: Trio whole-exome sequencing and Sanger validation were performed on the proband and her parents. Candidate gene mutations were analyzed using the Genome Aggregation Database (gnomAD) for normal frequency distributions. The Human Splicing Finder (HSF) and Rare Disease Data Center (RDDC) RNA splicer algorithms predicted the variant's harmfulness, verified by a Minigene assay. RESULTS: The proband had a heterozygous SF3B2 variant, NM_006842.3:c.777+1G>A. The patient's father also carried this variant and exhibited facial abnormalities. The variant was not in gnomAD, and HSF and RDDC RNA splicers indicated donor site disruption. The minigene assay suggested that two mRNA products were produced, leading to a premature termination codon. CONCLUSION: For this family, the pathogenesis of CFM may have been caused by an SF3B2 splicing variant. Affected family members exhibited varying degrees of malformation, indicating that CFM has phenotypic heterogeneity. This finding expands the phenotype and variant spectrum of SF3B2, enriches neonatal CFM research, and provides a possible guide to genetic counseling.

Diffusion tensor imaging analysis of the corpus callosum in children with high-risk autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that begins in early infancy and childhood and is characterized by impaired social communication and repetitive stereotyped behaviors. OBJECTIVE: The purpose of this study was to examine the development of the corpus callosum and its relationship to neurobehavior in young children with high-risk (HR) ASD using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: Twenty-one children with HR-ASD who visited Anhui Children's Hospital between January 2020 and December 2021 were selected as the study group, while 19 matched children with normal development during the same time were adopted as the control group. Cranial MRI+DTI were performed for all of the enrolled children and fractional anisotropy (FA) measurements were taken in each region of the corpus callosum. RESULTS: The FA values in all regions of the corpus callosum were higher in the study group than in the control group (0.417 ± 0.016 vs. 0.412 ± 0.02 in the corpus callosum knee, 0.439 ± 0.018 vs. 0.431 ± 0.023 in the corpus callosum body, and 0.446 ± 0.017 vs. 0.434 ± 0.019 in the splenium of corpus callosum [SCC]), where the difference in the FA in the SCC was statistically significant between the two groups (P< 0.05). There was a positive correlation between the FA in the corpus callosum knee and speech scores in the neuropsychological development of the study group (P< 0.05). CONCLUSION: There was a premature development tendency for corpus callosum myelination in young children with HR-ASD, and the developmental tendency was visible in the SCC. There was also a positive relationship between corpus callosum knee development and language function.