The Effect of Combined Growth Hormone and a Gonadotropin-Releasing Hormone Agonist Therapy on Height in Korean 3-M Syndrome Siblings
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
3-M syndrome is a rare autosomal recessive growth disorder characterized by severe growth retardation, low birth weight, characteristicfacial features, and skeletal anomalies, for which three causative genes (CUL7, OBSL1, and CCDC8) have been identified. We herein report two Korean siblings with 3-M syndrome caused by two novel OBSL1 mutations, and describe the effect of acombined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist. A 7-year-old girl withshort stature (-3.37 standard deviation score, SDS) and breast budding presented with subtle dysmorphic features, includingmacrocephaly, frontal bossing, a triangular face, prominent philtrum, full lips, a short neck, and fifth-finger clinodactyly. GnRHstimulation test revealed a pubertal pattern and advanced bone age of 8 years and 10 months. Her older sister, aged 10 years and9 months, had experienced an early menarche, and had an advanced bone age (13.5 years) and predicted adult height of 142 cm(-4.04 SDS). Targeted exome sequencing identified that the siblings had two heteroallelic mutations in OBSL1. Both siblings underwenta combination therapy with GH and a GnRH agonist. A height gain was noted in both siblings even after short-termtreatment. To fully elucidate the effects of the combined therapy, a larger cohort should be analyzed following a longer treatmentperiod. However, such an analysis would be challenging due to the rarity of this disease.
Abstract
3-M syndrome is a rare autosomal recessive growth disorder characterized by severe growth retardation, low birth weight, characteristicfacial features, and skeletal anomalies, for which three causative genes (CUL7, OBSL1, and CCDC8) have been identified. We herein report two Korean siblings with 3-M syndrome caused by two novel OBSL1 mutations, and describe the effect of acombined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist. A 7-year-old girl withshort stature (-3.37 standard deviation score, SDS) and breast budding presented with subtle dysmorphic features, includingmacrocephaly, frontal bossing, a triangular face, prominent philtrum, full lips, a short neck, and fifth-finger clinodactyly. GnRHstimulation test revealed a pubertal pattern and advanced bone age of 8 years and 10 months. Her older sister, aged 10 years and9 months, had experienced an early menarche, and had an advanced bone age (13.5 years) and predicted adult height of 142 cm(-4.04 SDS). Targeted exome sequencing identified that the siblings had two heteroallelic mutations in OBSL1. Both siblings underwenta combination therapy with GH and a GnRH agonist. A height gain was noted in both siblings even after short-termtreatment. To fully elucidate the effects of the combined therapy, a larger cohort should be analyzed following a longer treatmentperiod. However, such an analysis would be challenging due to the rarity of this disease.
참고문헌 (14)
- Clayton PE, "Exploring the spectrum of 3-M syndrome, a primordial short stature disorder of disrupted ubiquitination", Clin Endocrinol(Oxf), 77, pp.335~342 (2012)
- Hanson D, "Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling", J Mol Endocrinol, 49, pp.267~275 (2012)
- Hanson D, "The genetics of 3-M syndrome : unravelling a potential new regulatory growth pathway", Horm Res Paediatr, 76, pp.369~378 (2011)
- Huber C, "The 3M syndrome", Best Pract Res Clin Endocrinol Metab, 25, pp.143~151 (2011)
- Hanson D, "Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth", Am J Hum Genet, 89, pp.148~153 (2011)
- Huber C, "A large-scale mutation search reveals genetic heterogeneity in 3M syndrome", Eur J Hum Genet, 17, pp.395~400 (2009)
- Al-Dosari MS, "3M syndrome : an easily recognizable yet underdiagnosed cause of proportionate short stature", J Pediatr, 161, pp.139~145 (2012)
- Hanson D, "The primordial growth disorder 3-M syndrome connects ubiquitination to the cytoskeletal adaptor OBSL1", Am J Hum Genet, 84, pp.801~806 (2009)
- Huber C, "OBSL1 mutations in 3-M syndrome are associated with a modulation of IGFBP2 and IGFBP5 expression levels", Hum Mutat, 31, pp.20~26 (2010)
- Demir K, "Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation", J Pediatr Endocrinol Metab, 26, pp.147~150 (2013)
- Keskin M, "A rare cause of short stature : 3M syndrome in a patient with novel mutation in OBSL1 gene", J Clin Res Pediatr Endocrinol, 9, pp.91~94 (2017)
- Simsek-Kiper PO, "Further expanding the mutational spectrum and investigation of genotype-phenotype correlation in 3M syndrome", Am J Med Genet A, 179, pp.1157~1172 (2019)
- Guo MH, "Whole exome sequencing to identify genetic causes of short stature", Horm Res Paediatr, 82, pp.44~52 (2014)
- Akawi NA, "Is autosomal recessive Silver-Russel syndrome a separate entity or is it part of the 3-M syndrome spectrum", Am J Med Genet A (2011)