Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome
Authors:   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Zhang Hong-Yang , Wang Fei ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Tao Hai ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Tian Ya-Ping ,   Center for Birth Defects Prevention and Control Technology Research and Innovation, Chinese PLA General Hospital, Beijing 100853, China, Zhou Xi-Bin ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Bai Fang ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Wang Peng ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China, Cui Jia-Yi ,   Center for Birth Defects Prevention and Control Technology Research and Innovation, Chinese PLA General Hospital, Beijing 100853, China, Zhang Min-Jie ,   Center for Birth Defects Prevention and Control Technology Research and Innovation, Chinese PLA General Hospital, Beijing 100853, China, Wang Li-Hua ,   Senior Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing 100039, China
Published: April 2023

AIM: To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome [LADD (MIM 149730)] showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.
METHODS: Ophthalmological examinations, including slit-lamp biomicroscopy and lacrimal duct probing, and computed tomography dacryocystography (CT-DCG) were performed for all participants. The family pedigree was drawn, genetic features were analyzed, and the genomic DNA of the subjects was extracted. Pathogenic genes were screened via whole exome sequencing (WES) and confirmed using Sanger sequencing.
RESULTS: Six patients belonged to this three-generation family, and their clinical manifestations included congenital nasolacrimal duct obstruction, congenital absence of lacrimal puncta and canaliculi, lacrimal fistulae, and limb deformities. This pattern indicates autosomal dominant inheritance. Diagnosis was based on the clinical characteristics of LADD syndrome, which presented in all the patients in this family. A novel frameshift mutation in the FGF10 gene (NM_004465.1), c.234dupC (p.Trp79Leus*15), was identified in all patients via WES. The variant was confirmed by Sanger sequencing and classified as a “pathogenic mutation” according to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines.
CONCLUSION: A novel frameshift mutation in the FGF10 gene is found in all patients. This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.