A family with X-linked Cornelia de Lange syndrome due to a novel SMC1A missense mutation identified by multi-gene panel sequencing
Cornelia de Lange syndrome (CdLS) is a rare, clinically and genetically heterogeneous, multi-system developmental disorder caused by mutations in genes that encode components of the cohesin complex. X-linked CdLS caused by an SMC1A mutation is an extremely rare disease characterized by phenotypes milder than those of classic CdLS. In the Republic of Korea, based on a literature review, one family with SMC1A-related CdLS with mild phenotypes has been genetically confirmed to date. In this study, we describe the clinical features of a Korean boy with a hemizygous novel missense mutation and his mother with a heterozygous mutation, i.e., c.2447G>A (p.Arg816His) in SMC1A, identified by multi-gene panel sequencing. The proband had a mild phenotype with typical facial features and his mother exhibited a mild, subclinical phenotype. This study expands the clinical spectrum of patients with X-linked CdLS caused by SMC1A variants. Moreover, these findings reinforce the notion that a dominant negative effect in a carrier female with a heterozygous mutation in SMC1A results in a phenotype milder than that in a male patient with the same mutation.
- Ansari M, Poke G, Ferry Q, Williamson K, Aldridge R, Meynert AM, et al. Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism. J Med Genet 2014;51:659-68.
- Boyle MI, Jespersgaard C, Brondum-Nielsen K, Bisgaard AM, Tumer Z. Cornelia de Lange syndrome. Clin Genet 2015;88:1-12.
- Liu J, Krantz ID. Cornelia de Lange syndrome, cohesin, and beyond. Clin Genet 2009;76:303-14.
- Borck G, Zarhrate M, Bonnefont JP, Munnich A, Cormier-Daire V, Colleaux L. Incidence and clinical features of X-linked Cornelia de Lange syndrome due to SMC1L1 mutations. Hum Mutat 2007;28:205-6.
- Huisman S, Mulder PA, Redeker E, Bader I, Bisgaard AM, Brooks A, et al. Phenotypes and genotypes in individuals with SMC1A variants. Am J Med Genet A 2017;173:2108-25.
- Musio A, Selicorni A, Focarelli ML, Gervasini C, Milani D, Russo S, et al. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations. Nat Genet 2006;38:528-30.
- Deardorff MA, Kaur M, Yaeger D, Rampuria A, Korolev S, Pie J, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet 2007;80:485-94.
- Mannini L, Cucco F, Quarantotti V, Krantz ID, Musio A. Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome. Hum Mutat 2013;34:1589-96.
- Jang MA, Lee CW, Kim JK, Ki CS. Novel pathogenic variant (c.3178G>A) in the SMC1A gene in a family with Cornelia de Lange syndrome identified by exome sequencing. Ann Lab Med 2015;35:639-42.
- Liu J, Feldman R, Zhang Z, Deardorff MA, Haverfield EV, Kaur M, et al. SMC1A expression and mechanism of pathogenicity in probands with X-linked Cornelia de Lange syndrome. Hum Mutat 2009;30:1535-42.
- Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. 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 2015;17:405-24.
- Gervasini C, Russo S, Cereda A, Parenti I, Masciadri M, Azzollini J, et al. Cornelia de Lange individuals with new and recurrent SMC1A mutations enhance delineation of mutation repertoire and phenotypic spectrum. Am J Med Genet A 2013;161A:2909-19.
- NDSL :
- DOI : http://dx.doi.org/10.5734/JGM.2018.15.1.24
- 원문이 없습니다.
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.
- 이 논문과 함께 출판된 논문 + 더보기