Pedigree analysis of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene
10.3760/cma.j.cn311282-20210803-00490
- VernacularTitle:SLC40A1基因c.430A>G杂合突变的Ⅳ型遗传性血色病一家系的临床研究
- Author:
Shuai ZHENG
1
;
Yun SHI
;
Chengcheng ZHAO
;
Fan YANG
;
Hongwen ZHOU
;
Tao YANG
;
Xuqin ZHENG
Author Information
1. 南京医科大学第一附属医院内分泌科 210029
- Keywords:
Hereditary hemochromatosis, type Ⅳ;
SLC40A1 gene;
Ferritin;
Hypogonadism
- From:
Chinese Journal of Endocrinology and Metabolism
2022;38(3):208-213
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate clinical phenotypes of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene and the correlation between genotype and phenotype, exploring ferritin cutoff value for screening.Methods:One case of type Ⅳ hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene and 5 generations of their family lineage with a total of 47 members who were seen at the First Affiliated Hospital of Nanjing Medical University in July 2020 were studied for systematic clinical investigation. Thirty-nine surviving individuals were tested for ferritin, liver function, fasting plasma glucose (FPG), and sex hormones, and Sanger sequencing was performed to verify the mutation loci and to map the family tree. Spearman correlation analysis was used to explore the relationship between ferritin and other indicators, and receiver operating characteristic curves were used to calculate the ferritin cutoff value for screening for this genotype of hemochromatosis.Results:Ten patients with c. 430A>G heterozygous mutation in the SLC40A1 gene were identified among 39 family members, and five of them were diagnosed with hemochromatosis, presenting incomplete penetrance. The differences in levels of ferritin, aspartate aminotransferase (AST; both P<0.01) and FPG, as well as incidences of hypogonadotropic hypogonadism and arthritis (all P<0.05) between group of mutation positive and group negative were statistically significant, while the difference in alanine aminotransferase (ALT) was not. Spearman correlation analysis showed that, ferritin levels were significantly associated with ALT ( r=0.903), AST ( r=0.879), FPG ( r=0.782), and the incidences of hypogonadotropic hypogonadism ( r=0.798) and arthritis ( r=0.798; all P<0.01) in those with the c. 430A>G heterozygous mutation in the SLC40A1 gene. The ferritin cutoff value for screening of hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene was 1 036.7 μg/L, with a sensitivity and specificity of 100% and 94.3%, respectively. Conclusion:The SLC40A1 gene c. 430A>G heterozygous mutation is closely associated with elevated levels of AST and FPG, increased incidences of hypogonadotropic hypogonadism and arthritis, and the ferritin cutoff value is a useful screening parameter.
