Maternal Uniparental Disomy for Chromosome 20: Physical and Endocrinological Characteristics of Five Patients

• Published in: The journal of clinical endocrinology and metabolism Vol. 103; no. 6; pp. 2083 - 2088
• Main Authors: Kawashima, Sayaka, Nakamura, Akie, Inoue, Takanobu, Matsubara, Keiko, Horikawa, Reiko, Wakui, Keiko, Takano, Kyoko, Fukushima, Yoshimitsu, Tatematsu, Toshi, Mizuno, Seiji, Tsubaki, Junko, Kure, Shigeo, Matsubara, Yoichi, Ogata, Tsutomu, Fukami, Maki, Kagami, Masayo
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.06.2018; Copyright Oxford University Press; Oxford University Press
• Subjects: Age; Calcium - blood; Child; Child, Preschool; Chromogranins - genetics; Chromosome 20; Chromosomes; Chromosomes, Human, Pair 20; Etiology; Feeding; Female; Gestational age; GTP-Binding Protein alpha Subunits, Gs - genetics; Humans; Hypercalcemia; Hypersensitivity; Male; Molecular chains; Mothers; Parathyroid; Parathyroid hormone; Parathyroid Hormone - blood; Patients; Phenotype; Silver-Russell Syndrome - blood; Silver-Russell Syndrome - diagnosis; Silver-Russell Syndrome - genetics; Small for gestational age; Thyroid; Thyroid-stimulating hormone; Underpotential deposition; Uniparental Disomy
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2017-02780

Abstract 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. Maternal uniparental disomy for chromosome 20 may account for >5% of cases with etiology-unknown Silver-Russell syndrome and can be associated with hypersensitivity of hormone receptors.