TY - JOUR
T1 - Frequency and clinical characteristics of distinct etiologies in patients with Silver-Russell syndrome diagnosed based on the Netchine-Harbison clinical scoring system
AU - Fuke, Tomoko
AU - Nakamura, Akie
AU - Inoue, Takanobu
AU - Kawashima, Sayaka
AU - Hara-Isono, Kaori
AU - Matsubara, Keiko
AU - Sano, Shinichiro
AU - Yamazawa, Kazuki
AU - Fukami, Maki
AU - Ogata, Tsutomu
AU - Kagami, Masayo
N1 - Funding Information:
We are grateful to the patients and their families for their cooperation. This work was supported by grants from the Japan Agency for Medical Research and Development (AMED) (20ek0109373h0003), the National Center for Child Health and Development (28-6, 2019B-4), the Foundation for Growth Science, and the Takeda Science Foundation.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
PY - 2022/10
Y1 - 2022/10
N2 - Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the “SRS spectrum”.
AB - Silver-Russel syndrome (SRS) is a representative imprinting disorder (ID) characterized by growth failure and diagnosed by clinical features. Recently, international consensus has recommended using the Netchine-Harbison clinical scoring system (NH-CSS) as clinical diagnostic criteria. Loss of methylation of H19/IGF2:intergenic differentially methylated region (H19LOM) and maternal uniparental disomy chromosome 7 (UPD(7)mat) are common etiologies of SRS; however, other IDs, pathogenic variants (PVs) of genes, and pathogenic copy number variants (PCNVs) have been reported in patients meeting NH-CSS. To clarify the frequency and clinical characteristics of each etiology, we conducted (epi)genetic analysis in 173 patients satisfying NH-CSS. H19LOM and UPD(7)mat were identified in 34.1%. PCNVs, other IDs, and PVs were in 15.0%. Patients with all six NH-CSS items were most frequently observed with H19LOM and UPD(7)mat. This study confirmed the suitability of NH-CSS as clinical diagnostic criteria, the (epi)genetic heterogeneity of SRS, and showed the necessity of further discussion regarding the “SRS spectrum”.
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U2 - 10.1038/s10038-022-01048-7
DO - 10.1038/s10038-022-01048-7
M3 - Article
C2 - 35606504
AN - SCOPUS:85130517977
SN - 1434-5161
VL - 67
SP - 607
EP - 611
JO - Jinrui idengaku zasshi. The Japanese journal of human genetics
JF - Jinrui idengaku zasshi. The Japanese journal of human genetics
IS - 10
ER -