Clinical and genetic features of dyskeratosis congenita, cryptic dyskeratosis congenita, and Hoyeraal-Hreidarsson syndrome in Japan.
Dyskeratosis congenita (DKC) is an inherited bone marrow failure (BMF) syndrome typified by reticulated skin pigmentation, nail dystrophy, and mucosal leukoplakia. Hoyeraal-Hreidarsson syndrome (HHS) is considered to be a severe form of DKC. Unconventional forms of DKC, which develop slowly in adulthood but without the physical anomalies characteristic of DKC (cryptic DKC), have been reported. Clinical and genetic features of DKC have been investigated in Caucasian, Black, and Hispanic populations, but not in Asian populations. The present study aimed to determine the clinical and genetic features of DKC, HHS, and cryptic DKC among Japanese patients. We analyzed 16 patients diagnosed with DKC, three patients with HHS, and 15 patients with cryptic DKC. We found that platelet count was significantly more depressed than neutrophil count or hemoglobin value in DKC patients, and identified DKC patients with large deletions in the telomerase reverse transcriptase and cryptic DKC patients with RTEL1 mutations on both alleles. This led to some patients previously considered to have unclassifiable BMF being diagnosed with cDKC through identification of new gene mutations. It thus seems important from a clinical viewpoint to re-examine the clinical characteristics, frequency of genetic mutations, and treatment efficacy in DKC, HHS, and cDKC.
Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan. y-hiroki@fd6.so-net.ne.jp.
Hiroki
H
Yamaguchi
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Hirotoshi
H
Sakaguchi
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Konoechyou, Yoshida, Sakyou-ku, Kyoto, 606-8501, Japan.
Kenichi
K
Yoshida
Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, 143 Shitakasuya, Isehara, 259-1193, Japan.
Miharu
M
Yabe
Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, 143 Shitakasuya, Isehara, 259-1193, Japan.
Hiromasa
H
Yabe
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Yusuke
Y
Okuno
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Hideki
H
Muramatsu
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Yoshiyuki
Y
Takahashi
Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan.
Shunsuke
S
Yui
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.
Yuichi
Y
Shiraishi
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.
Kenichi
K
Chiba
Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.
Hiroko
H
Tanaka
Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.|Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, 108-8639, Japan.
Satoru
S
Miyano
Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan.
Koiti
K
Inokuchi
Department of Pediatrics, Hirosaki University Graduate School of Medicine, 53 Honchyou, Hirosaki, 036-8563, Japan.
Etsuro
E
Ito
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Konoechyou, Yoshida, Sakyou-ku, Kyoto, 606-8501, Japan.
Seishi
S
Ogawa
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Seiji
S
Kojima
D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D019871:Dyskeratosis Congenita / Q000097:blood / Q000235:genetics / Q000628:therapy; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000235:genetics / Q000628:therapy; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000097:blood / Q000235:genetics / Q000628:therapy; D007564:Japan; D008297:Male; D008831:Microcephaly / Q000097:blood / Q000235:genetics / Q000628:therapy; D009154:Mutation; D010976:Platelet Count
C532890:RTEL1 protein, human; D004265:DNA Helicases
Bone marrow failure; Cryptic dyskeratosis congenita; Dyskeratosis congenita; Genetic feature; Hoyeraal-Hreidarsson syndrome