Abstract: Objective: To report a case of hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP), and to detect gene mutations in the patient and their family. Methods: The clinical data of the child patient were collected, and a physical examination was conducted. Peripheral blood samples were collected from the patient and their parents, and genomic DNA was extracted. High-throughput sequencing technology was used to screen genes related to hereditary skin diseases, and Sanger sequencing was employed to verify candidate mutation sites. Protein structure prediction software was applied to evaluate the potential impact of the mutation on the structure of the FAM111B protein. Results: The patient presented with abnormal skin pigmentation, sparse eyebrows, and cholestasis, while the patient's mother showed the same skin lesion manifestations. A heterozygous mutation c.1883G＞A (p.Ser628Asn) was detected in the FAM111B gene of the patient; the patient's mother also carried the same heterozygous variant, whereas the patient's father did not. This variant was not detected in 100 unrelated healthy controls. Analysis of the protein site structure revealed that the p.Ser628Asn variant could alter the chemical properties of the amino acid side chain, leading to weakened hydrogen bond interaction between the newly formed Asn628 and the adjacent Thr625 residue after the mutation. Conclusion: Both the child patient and their mother carry the heterozygous mutation c.1883G＞A (p.Ser628Asn) in the FAM111B gene, which is the pathogenic gene for this family.

Key words: FAM111B gene, POIKTMP, genetic screening