신경섬유종증 1형: 두개의 새로운 돌연변이에 대한 보고
Neurofibromatosis Type I: Case Reports of Two Novel Mutations
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
신경섬유종증 1형(NF1)은 피부에 나타나는 밀크커피색 반점, 겨드랑이와 서혜부의 주근깨, 홍채의 Lisch 결절, 신경섬유종 등을 특징으로 한다. 신경섬유종증 1형이 의심되는 환자에서 NF1 유전자의 58개의 엑손과 주변 인트론에 대하여 염기서열분석을 실시하였다. 이를 통해 2명의 환자에서 병원성으로 판단되는 이전에 보고되지 않은 틀이동돌연변이를 검출하였다. 환자1은 59세 남자 환자로 신경섬유종과 가족력이 있었고, 오른쪽 엉덩뼈에 양성 종양, 오른쪽 부신에 양성종양, 좌측 소뇌에 별아교세포종이 발견되었고, 3108번 핵산에 A염기의 이형 결실 돌연변이(c.3108delA; p.Lys1036Asnfs*14)가 발견되었다. 환자2는 25개월 여아로 가족력과 밀크커피색 반점이 있었고, 7623번 핵산에 G염기의 이형 결실돌연변이(c. 7623delG; p.Ile2541Serfs*7)의 틀이동돌연변이가 발견되었다. 새로운 변이의 보고를 통해 신경섬유종증 1형 환자와 가족의 유전상담과 임상관리에 유용하게 사용될 수 있겠다.
Abstract
Neurofibromatosis type 1 (NF1) is characterized by multiple café-au-lait spots, axillary and inguinal freckling, Lisch nodules in the iris, and fibromatous tumors of the skin. We performed direct sequencing of 58 exons comprising the NF1 gene along with the associated intronic regions in suspected cases of NF1. We have detected two different novel frameshift mutations in two cases, respectively. The first case involved a 59-year-old male presenting with neurofibromas and a positive family history of NF1. The patient presented with leiomyomas of the iliac bone and right adrenal gland, and an astrocytoma of the left cerebellum. The mutation in this patient was caused by heterozygous deletion of base A at nucleotide position 3108 (c.3108delA; p.Lys1036Asnfs*14). The second case involved a 25-month-old girl presenting with multiple café-au-lait spots and a positive family history of NF1. The mutation in this patient was caused by heterozygous deletion of base G at nucleotide position 7623 (c.7623delG;p.Ile2541Serfs*7). These novel mutations may be useful for advanced genetic counseling and clinical management of patients with NF1 and their families.
참고문헌 (19)
- Cawthon RM, "A major segment of the neurofibromatosis type 1 gene : cDNA sequence, genomic structure, and point mutations", Cell, 62, pp.193~201 (1990)
- Williams VC, "Neurofibromatosis type 1 revisited", Pediatrics, 123, pp.124~133 (2009)
- Easton DF, "An analysis of variation in expression of neurofibromatosis(NF)type 1(NF1) : evidence for modifying genes", Am J Hum Genet, 53, pp.305~313 (1993)
- Evans DG, "Birth incidence and prevalence of tumor-prone syndromes : estimates from a UK family genetic register service", Am J Med Genet A, 152A, pp.327~332 (2010)
- Richards S, "ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology", Genet Med, 17, pp.405~424 (2015)
- Shen MH, "Molecular genetics of neurofi-bromatosis type 1(NF1)", J Med Genet, 33, pp.2~17 (1996)
- Wallace MR, "Type 1 neurofibromatosis gene : identification of a large transcript disrupted in three NF1 patients", Science, 249, pp.181~186 (1990)
- "Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference", Arch Neurol, 45, pp.575~578 (1988)
- "Synonyms: NF1, Von Recklinghausen Disease, Von Recklinghausen’s Neurofibromatosis" (2019)[URL]
- Mautner VF, "Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1. 4 Mb type-1 NF1 deletions", J Med Genet, 47, pp.623~630 (2010)
- Pasmant E, "NF1 microdeletions in neurofibromatosis type 1 : from genotype to phenotype", Hum Mutat, 31, pp.E1506~E1518 (2010)
- Kehrer-Sawatzki H, "Neurofibromatosis Type 1", pp.187~209 (2012), Springer-Verlag
- Upadhyaya M, "An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene(c. 2970-2972 delAAT) : evidence of a clinically significant NF1 genotype-phenotype correlation", Am J Hum Genet, 80, pp.140~151 (2007)
- Pinna V, "p. Arg1809Cys substitution in neurofibromin is associated with a distinctive NF1 phenotype without neurofibromas", Eur J Hum Genet, 23, pp.1068~1071 (2015)
- Rojnueangnit K, "High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p. Arg1809 : genotype-phenotype correlation", Hum Mutat, 36, pp.1052~1063 (2015)
- "The Human Gene Mutation Database"[URL]
- Kang E, "Phenotype categorization of neurofibromatosis type I and correlation to NF1 mutation types", J Hum Genet, 65, pp.79~89 (2020)
- Ko JM, "Mutation spectrum of NF1 and clinical characteristics in 78 Korean patients with neurofi-bromatosis type 1", Pediatr Neurol, 48, pp.447~453 (2013)
- Pasmant E, "Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you have a large gene with loss of function mutations?", Eur J Hum Genet, 23(5), pp.596~601 (2015)