RESUMO
This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden of de novo variants in our selected candidate genes within the unsolved NDD cohort and identified qualifying de novo variants in seven candidate genes: RIF1, CAMK2D, RAB11FIP4, AGO3, PCBP2, LEO1, and VCP. Clinical data were collected from six new individuals with de novo or inherited LEO1 variants and three new individuals with de novo PCBP2 variants. Our findings add additional evidence for LEO1 as a risk gene for autism and intellectual disability. Furthermore, we prioritize PCBP2 as a candidate gene for NDD associated with motor and language delay. In summary, by leveraging de novo burden analysis studies, employing a stringent variant filtering pipeline, and engaging in targeted patient recruitment, our study contributes to the identification of novel genes implicated in NDDs.
RESUMO
BACKGROUND: Pediatric germ cell tumors account for approximately 3.5 % of all childhood cancers for children under the age of 15 years. Up to one-third are extragonadal neoplasms. Germ cell tumors are a heterogeneous group of malignant tumors with a wide variety of histopathological features. Yolk sac tumor is the predominant variant in newborns and younger children. We report for the first time, the presentation of a primary yolk sac tumor in the abdominal wall of a small child. CASE PRESENTATION: An 18-month-old white girl underwent resection of a small, round subcutaneous lump (1.5×1.3×0.8 cm) of the abdominal wall in her right hypochondriac region. The histopathology was compatible with yolk sac tumor. Her alpha-fetoprotein was initially elevated but normalized after the resection. Magnetic resonance imaging of her abdomen was normal. The surgeon decided to observe and follow her alpha-fetoprotein level closely. One year after resection a local recurrence appeared and her alpha-fetoprotein rose to 58 ng/mL. The surgeon performed a wide resection of the lesion with normalization of her alpha-fetoprotein. Follow-up consisted of measuring alpha-fetoprotein, clinical evaluation, and abdominal ultrasound. CONCLUSIONS: Clinicians should be aware that a yolk sac tumor can present in an unusual extragonadal place, for example in this case it was subcutaneous. In some cases, conservative treatment can be carried out with careful monitoring of the patient and their alpha-fetoprotein.