Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3

Infante, Elena; Alkorta‐Aranburu, Gorka; El-Gharbawy, Areeg

doi:10.1002/ccr3.1010

Cited by 6 publications

(5 citation statements)

References 21 publications

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“…An online database search was conducted on PubMed and Web of Science databases using "SMC3" and "Cornelia de Lange syndrome" as the keywords. The search yielded 45 cases of CdLS, with definite variants of SMC3 reported as of July 2023, of which 24 cases had detailed clinical data (including the two cases in our study) (Figure 7) (Ansari et al, 2014;Bowling et al, 2017;Deardorff et al, 2007Deardorff et al, , 2012"Deciphering Developmental Disorders Study", 2017;Dowsett et al, 2019;Gao et al, 2019;Gil-Rodríguez et al, 2015;Infante et al, 2017;Kaur et al, 2016;Kosmicki et al, 2017;Kruszka et al, 2019;Li et al, 2021;Liu et al, 2020;Rentas et al, 2020;Retterer et al, 2016;Sanders et al, 2012;Stanley et al, 2020;Stessman et al, 2017;Stranneheim et al, 2021;Turner et al, 2019;Yuan et al, 2015Yuan et al, , 2019. No instances of these cases were observed within consanguineous families.…”

Section: Discussionmentioning

confidence: 92%

“…The former had mild intellectual disability, while the latter showed severe intellectual disability. In addition, Infante et al (2017) reported a mother and her daughter carrying the same SMC3 variant (c.1433_1435dup), and the mother, who had mild symptoms, was not diagnosed until the pathogenic variant was identified in her child. The affected child had clinical features such as microcephaly, arched thick eyebrows, hirsutism, synophrys, mild ptosis, flat nasal bridge, a small chin with mild retrognathia, proximally placed thumbs, hypotonia, feeding difficulties, and growth retardation.…”

Section: Discussionmentioning

confidence: 99%

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Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome

Lei,

Song,

Zheng

et al. 2024

Molec Gen & Gen Med

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BackgroundCornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families.MethodsClinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio‐based whole‐exome sequencing. Pyrosequencing, chip‐based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants.ResultsNovel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies.ConclusionBoth patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome

Lei,

Song,

Zheng

et al. 2024

Molec Gen & Gen Med

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“…Genetic tests do not always yield diagnostic results, as the condition is with multifactor genetic etiology and a universal genetic defect has not yet been identified [2,3,6,11].…”

Section: Discussionmentioning

confidence: 99%

Parenchymal Organ Changes in Two Female Patients With Cornelia de Lange Syndrome: Autopsy Case Report

Mangelov

Balgarinova

Zaykova

et al. 2020

Cureus

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“…All cases of CdLS (up to February 1st, 2020) were collected from the PubMed and Web of Science databases using the keywords "Cornelia de Lange syndrome", and the identified papers were carefully reviewed to include all relevant papers (9)(10)(11)(12)(13)(14)(15)(16). The clinical manifestations and genetic results of all cases reported were analyzed and summarized by using SPSS version 25.0.…”

Section: Literature Review and Statistical Analysismentioning

confidence: 99%

A Chinese Case of Cornelia de Lange Syndrome Caused by a Pathogenic Variant in SMC3 and a Literature Review

Tian

Liang

et al. 2021

Front. Endocrinol.

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PurposeCornelia de Lange syndrome (CdLS) is a rare congenital developmental disorder, and cases caused by variants in SMC3 are infrequent. This article describes a case of CdLS related to a pathogenic variant in SMC3 and performs a literature review.MethodsWe collected clinical data and biological samples from a 12-year-old boy with “short stature for 11 years”. Gene variants in the proband were detected by whole-exome sequencing, and the variants in his parents were verified by Sanger sequencing. All SMC3-related CdLS patients from the PubMed and Web of Science databases were collected and summarized using the available data.ResultsA pathogenic variant in SMC3 in the proband, c.1942A>G, was identified. Neither of his parents carried the same variant. Twenty-eight patients were diagnosed with CdLS with variants in SMC3, including the cases in this study and those reported in the literature, where half of the variant types were missense, followed by 32% (9/28) with a deletion and 11% (3/28) with a duplication. All patients showed symptoms of verbal development delay and intellectual disability to different degrees, and 90% patients had long eyelashes while 89% patients had arched eyebrows.ConclusionThis study summarized different gene variants in SMC3 and the frequencies of the various clinical manifestations according to the reported literature. For CdLS caused by SMC3 variants, short stature and facial dysmorphic features are the two most important clinical clues. Definite diagnosis of this rare disease may be challenging clinically; thus, it is significant to use molecular diagnosis.

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Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3

Cited by 6 publications

References 21 publications

Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome

Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome

Parenchymal Organ Changes in Two Female Patients With Cornelia de Lange Syndrome: Autopsy Case Report

A Chinese Case of Cornelia de Lange Syndrome Caused by a Pathogenic Variant in SMC3 and a Literature Review

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