Objective Design short stature panel with gene curration strategy.Methods The gene curation process was introduced in detail.The strength of a gene-disease relationship was evaluated based on publicly available genetic and experimental evidence.This process in short stature panel design and its effect on gene selection was further demonstrated.Results After gene curation, the number of gene in list was effectively decreased from 1 276 to 705.The panel sequencing reached a diagnosis rate of 19.7% among a cohort of 371 nation-wide ascertained short stature patients.The gene curation process reduced the risk of false positive findings and decreased diagnostic cost and working hours without affecting the diagnosis rate.Conclusion Gene curation is an important step for NGS-based test and should be widely exercised.

Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.