Jing Chen1, Jiangfei Yang2, Suzhou Zhao3, Hui Ying4, Guimei Li5, Chao Xu6. 1. Department of Child Health, Xiamen Maternal and Child Health Hospital, Xiamen, Fujian, China; Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. 2. Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. 3. Sinopath Diagnostics, Tongzhou District, Beijing, China. 4. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China. 5. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: chenjing8469899@126.com. 6. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, China. Electronic address: doctorxuchao@163.com.
Abstract
BACKGROUND: Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early. MATERIALS AND METHODS: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis. RESULTS: The proband and his mother all presented disproportionate short stature, short, stubby extremities, unchanged interpedicular distances from L1-L5, and short iliac bones, with a 'fish mouth-shaped' sciatic notch. The mother received induced abortion recently because an ultrasound showed short femur length of her fetus at 24-week gestation. Eventually, a novel heterozygous mutation (c.1145G>A) in FGFR3 was identified by TES in the proband, his mother, and her fetus; this causes the substitution of glycine with aspartic acid in codon 382. CONCLUSIONS: In this study, we diagnosed a Chinese pedigree with HCH based on clinical data, radiographic features, and genetic testing results. Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.
BACKGROUND:Hypochondroplasia (HCH; OMIM 146000) is a common autosomal dominant skeletal dysplasia characterized by disproportionate short stature, short extremities, relative macrocephaly, and lumbar lordosis. Because of its clinical and genetic heterogeneity, gene mutational analysis is particularly important in diagnosis and the phenotypes may be ameliorated if diagnosed early. MATERIALS AND METHODS: In this study, we examined a Chinese family with HCH, performed an inductive analysis of their clinical features and radiographic results, and applied targeted exome sequencing (TES) technology to perform a molecular diagnosis. RESULTS: The proband and his mother all presented disproportionate short stature, short, stubby extremities, unchanged interpedicular distances from L1-L5, and short iliac bones, with a 'fish mouth-shaped' sciatic notch. The mother received induced abortion recently because an ultrasound showed short femur length of her fetus at 24-week gestation. Eventually, a novel heterozygous mutation (c.1145G>A) in FGFR3 was identified by TES in the proband, his mother, and her fetus; this causes the substitution of glycine with aspartic acid in codon 382. CONCLUSIONS: In this study, we diagnosed a Chinese pedigree with HCH based on clinical data, radiographic features, and genetic testing results. Our results extend the genetic mutation spectrum of FGFR3 and demonstrate that TES is an effective method for the diagnosis of skeletal dysplasia in clinical practices.