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A novel locus for maternally inherited human gingival fibromatosis at chromosome 11p15

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Abstract

Human isolated gingival fibromatosis is an oral disorder characterized by a slowly progressive benign enlargement of gingival tissues. The most common genetic form, hereditary gingival fibromatosis (HGF), is usually transmitted as an autosomal dominant trait. We report here for the first time a newly identified maternally inherited gingival fibromatosis in two unrelated Chinese families and mapped this disease locus to human chromosome 11p15 with a maximum two point LOD score of 8.70 at D11S4046 (θ = 0) for family 1 and of 6.02 at D11S1318 for family 2. Haplotype analysis placed the critical region in the interval defined by D11S1984 and D11S1338. A cluster of maternally expressed genes is within this critical region. We screened individuals in these two families for mutations for all known maternally expressed genes within this region. None was found either within the coding sequence or at the intron–exon boundary of these genes. Neither did we detect any loss of imprinting in three informative imprinted genes including H19, KCNQ1 downstream neighbor (KCNQ1DN) and cyclin-dependent kinase inhibitor 1C (CDKN1C). However, gene expression profile analysis revealed reduced expression of hemoglobin beta (HBB), hemoglobin delta (HBD), hemoglobin gamma A (HBG1) and hemoglobin gamma G (HBG2) genes at disease locus in HGF patients. This study suggests that genome imprinting might affect the development of HGF.

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Abbreviations

HGF:

Hereditary gingival fibromatosis

DMR:

Differentially methylated region

H19DMR:

H19 differentially methylated region

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Acknowledgments

We gratefully acknowledge the contributions of the HGF families who participated in this study and have made this resource possible. Many thanks to all those individuals giving support to our work. We thank Y. Jiang and A. Ward for critical reading of this manuscript. This work is supported by the National High Technology Research and Development Program of China (863 Program) (No. 2001AA221091), the National Science Fund for Distinguished Young Scholars (No. 30125028), the National Natural Science Foundation of China, General Program (No. 30270728), Chinese Academy of Sciences (kscx2-sw-206), Shanghai Municipal Commission for Science and Technology (03DJ14010), and the Chinese National Key Program for Basic research (2004CB518603).

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Authors and Affiliations

  1. Health Science Institute, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Yufei Zhu, Yi Zhang, Yu Xia, Bo Li, Xiangyin Kong & Landian Hu

  2. Qingdao Haici Hospital, Qingdao, 266033, People’s Republic of China

    Wenxia Zhang

  3. Ningxia Medical College, Yinchuan, 750004, People’s Republic of China

    Zhenghao Huo

  4. State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University, 197 Rui Jin Road II, Shanghai, 200025, People’s Republic of China

    Xiangyin Kong

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  1. Yufei Zhu
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  2. Wenxia Zhang
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  3. Zhenghao Huo
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  4. Yi Zhang
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Correspondence to Xiangyin Kong or Landian Hu.

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Conflict Of Interest Statement: No competing financial interests.

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Zhu, Y., Zhang, W., Huo, Z. et al. A novel locus for maternally inherited human gingival fibromatosis at chromosome 11p15. Hum Genet 121, 113–123 (2007). https://doi.org/10.1007/s00439-006-0283-1

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