关键词: 酪氨酸血症, DNA突变分析, 系谱, 畏光, 皮肤角化病, 掌跖

Abstract: Su Ting, Wang Hongwei, Sun Weiling, Sun Yaqi, Lu Yan, Zhang Meihua, Cui Ting, Zhao Bian, Ge Yixin, Chen Yiwen, Su Zhonglan Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China （Su T, Sun WL, Sun YQ, Lu Y, Zhang MH, Zhao B, Ge YX, Chen YW, Su ZL）; Department of Laboratory, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China （Cui T）; Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China （Wang HW） Corresponding author: Su Zhonglan, Email: susustyle1990@163.com 【Abstract】 Objective To report a pedigree with tyrosinemia typeⅡ, and to analyze its causative mutations. Methods Clinical data were obtained from a 10?year?old male proband with tyrosinemia typeⅡ, and analyzed retrospectively. Blood and urine samples were collected from 19 persons in 3 generations of the pedigree, and the amino acid level was detected in these samples. Genomic DNA was extracted from all of the 19 family members, and mutations in the tyrosine aminotransferase （TAT） gene were detected. Results The patient developed photophobia at 2 months after birth, and the symptom was gradually aggravated after that. At the age of 6 years, ocular pain and photophobia occurred. At the age of 8 years, linear keratotic plaques occurred on his fingertips and soles of both feet, with obvious tenderness. Ophthalmic examination showed no obvious abnormalities in corneal staining or ocular fundus. Skin examination showed multiple linear keratotic plaques on the fingers and soles of both feet. The serum tyrosine level was 825.64 μmol/L, and the level of p?hydroxyphenyllactic acid in urine was 161.4 μmol/L. Genetic testing showed 2 novel mutations, including c.236G > A at position 236 in exon 2 of the TAT gene causing the substitution of glycine by glutamic acid （p.Gly79Glu）, and c.1141G > T at position 1141 in exon 10 of the TAT gene leading to the formation of a premature termination codon instead of glutamic acid （p.Glu381*）. The proband was the only patient in the family. Some members in the patrilineal family carried the mutation c.1141G > T （p.Glu381*）, and some in the maternal family carried the mutation c.236G > A （p.Gly79Glu）. Conclusion This is the first case of tyrosinemia typeⅡ reported in the domestic population, and 2 novel heterozygous mutations were identified in the TAT gene, which may lead to the occurrence of tyrosinemia typeⅡ in the patient.

Key words: Tyrosinemias, DNA mutational analysis, Pedigree, Photophobia, Keratoderma, palmoplantar