Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes.
This is a study of a patient who manifests all of the features of a diffuse leiomyomatosis-Alport syndrome (DL-ATS), and her two-year-old son who has already been diagnosed with Alport syndrome. Fourteen years ago, the patient underwent a partial esophageal resection followed by a replacement with jejunum. Recently, she underwent a surgical resection of the esophagus due to esophageal dysfunction. Genetic analyses of COL4A5 and COL4A6 on the X-chromosome were efficiently performed using the genomic DNA of her son. We have identified a novel deletion of 194-kb in length, encompassing COL4A5-COL4A6 promoters as well as nearly the entire large intron 1 of COL4A5 and intron 2 of COL4A6. To uncover the relationship of the esophagus-specific occurrence of the tumor and the expression of those genes, immunohistochemical analyses of type IV collagen α chains were conducted in the non-affected individuals. The esophageal smooth muscle-specific expression of α5(IV) and α6(IV) chains in the gastrointestinal tract was observed. Moreover, CAG repeat analysis of the androgen receptor gene and an immunohistochemical analysis in the leiomyoma revealed clonal overgrowth of the cells which received X-inactivation on the non-affected allele. These results may suggest that the dominant effect was caused by the partial deletion of the esophageal smooth muscle-specific genes, COL4A5 and COL4A6.
Oohashi
Toshitaka
T
Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
Naito
Ichiro
I
Ueki
Yasuyoshi
Y
Yamatsuji
Tomoki
T
Permpoon
Rattiya
R
Tanaka
Noriaki
N
Naomoto
Yoshio
Y
Ninomiya
Yoshifumi
Y
D001483:Base Sequence; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018231:Leiomyomatosis; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D009394:Nephritis, Hereditary / Q000235:genetics / Q000473:pathology; D055815:Young Adult
C478159:COL4A5 protein, human; C559044:COL4A6 protein, human; D024141:Collagen Type IV