TY - JOUR
T1 - Maternal Uniparental Disomy for Chromosome 20
T2 - Physical and Endocrinological Characteristics of Five Patients
AU - Kawashima, Sayaka
AU - Nakamura, Akie
AU - Inoue, Takanobu
AU - Matsubara, Keiko
AU - Horikawa, Reiko
AU - Wakui, Keiko
AU - Takano, Kyoko
AU - Fukushima, Yoshimitsu
AU - Tatematsu, Toshi
AU - Mizuno, Seiji
AU - Tsubaki, Junko
AU - Kure, Shigeo
AU - Matsubara, Yoichi
AU - Ogata, Tsutomu
AU - Fukami, Maki
AU - Kagami, Masayo
N1 - Funding Information:
This work was supported by grants from the Japan Society for the Promotion of Science (JSPS; 15K15096 and 17H06428), National Center for Child Health and Development (28-6), Japan Agency for Medical Research and Development (AMED;17ek0109278h0001, 16ek0109030h0003, and 16ek0109141h0002), the Takeda Science Foundation, and Japanese Society for Pediatric Endocrinology Future Development Grant.
Funding Information:
Financial Support: This work was supported by grants from the Japan Society for the Promotion of Science (JSPS; 15K15096 and 17H06428), National Center for Child Health and Development (28-6), Japan Agency for Medical Research and Development (AMED; 17ek0109278h0001, 16ek0109030h0003, and 16ek0109141h0002), the Takeda Science Foundation, and Japanese Society for Pediatric Endocrinology Future Development Grant.
Publisher Copyright:
© 2018 Endocrine Society.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Context Maternal uniparental disomy for chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. These patients manifested a phenotype similar to that of Silver-Russell syndrome (SRS) and small for gestational age-short stature (SGA-SS); however, the etiological relationship between UPD(20)mat and SRS/SGA-SS remains unclear. Moreover, no report has described endocrinological assessment of UPD(20)mat patients, although paternal UPD(20), the mirror image entity of UPD(20)mat, is known to cause multiple hormone resistance reflecting reduced α-subunit of the stimulatory G protein expression. Participants Patients 1 to 5 showed nonmosaic heterodisomy and/or isodisomy for the entire chromosome 20. Patients 1 to 3 and 4 were identified through UPD(20)mat screening for 55 patients with etiology-unknown SRS and 96 patients with SGA-SS, respectively. Patient 5 was identified through molecular analysis for patients with developmental defects. Patients 1 to 5 manifested postnatal growth failure and feeding problems, with or without developmental delay, and other clinical features. Patients 1 to 4 were born SGA. Patients 4 and 5 exhibited hypercalcemia and low or low-normal parathyroid hormone levels. Patient 1 showed constantly decreased thyroid-stimulating hormone (TSH) levels after 12 years of age, although she had a normal TSH level at 5.2 years of age. Conclusion The results suggest that UPD(20)mat underlies growth failure and feeding problems with additional features and could account for >5% of etiology-unknown SRS and small percentages of SGA-SS. Most important, this study provides an indication that UPD(20)mat can be associated with hypersensitivity of hormone receptors, which may gradually develop with age.
AB - Context Maternal uniparental disomy for chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. These patients manifested a phenotype similar to that of Silver-Russell syndrome (SRS) and small for gestational age-short stature (SGA-SS); however, the etiological relationship between UPD(20)mat and SRS/SGA-SS remains unclear. Moreover, no report has described endocrinological assessment of UPD(20)mat patients, although paternal UPD(20), the mirror image entity of UPD(20)mat, is known to cause multiple hormone resistance reflecting reduced α-subunit of the stimulatory G protein expression. Participants Patients 1 to 5 showed nonmosaic heterodisomy and/or isodisomy for the entire chromosome 20. Patients 1 to 3 and 4 were identified through UPD(20)mat screening for 55 patients with etiology-unknown SRS and 96 patients with SGA-SS, respectively. Patient 5 was identified through molecular analysis for patients with developmental defects. Patients 1 to 5 manifested postnatal growth failure and feeding problems, with or without developmental delay, and other clinical features. Patients 1 to 4 were born SGA. Patients 4 and 5 exhibited hypercalcemia and low or low-normal parathyroid hormone levels. Patient 1 showed constantly decreased thyroid-stimulating hormone (TSH) levels after 12 years of age, although she had a normal TSH level at 5.2 years of age. Conclusion The results suggest that UPD(20)mat underlies growth failure and feeding problems with additional features and could account for >5% of etiology-unknown SRS and small percentages of SGA-SS. Most important, this study provides an indication that UPD(20)mat can be associated with hypersensitivity of hormone receptors, which may gradually develop with age.
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U2 - 10.1210/jc.2017-02780
DO - 10.1210/jc.2017-02780
M3 - Article
C2 - 29878129
AN - SCOPUS:85048667901
VL - 103
SP - 2083
EP - 2088
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -