Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: Comments on the article by Pereza et al. [2012]

Pereza, Nina; Severinski, Srećko; Ostojić, Saša; Volk, Marija; Maver, Aleš; Dekanić, Kristina Baraba; Kapović, Miljenko; Peterlin, Borut

doi:10.1002/ajmg.a.36974

Cited by 8 publications

(4 citation statements)

References 7 publications

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“…In this report, we highlight that exostoses is most likely not associated to CdLS type 4 and RAD21 mutations but caused by EXTI deletions. Exostoses has recurrently been associated to heterozygous stop and missense mutations in EXT1 (MIM #133700) and has been reported in three CdLS patients (Deardorff et al, 2012;Pereza et al, 2015) with micro deletions spanning EXT1 (Figure 1D).…”

Section: Discussionmentioning

confidence: 84%

“…The lack of homozygous loss-of function variants in the normal population suggests that complete loss of RAD21 is lethal. Previously, eight unique heterozygous alterations of RAD21 variants have been reported in patients affected with CdLS type 4; three missense mutations (Deardorff et al, 2012;Martinez et al, 2017), two frameshift mutations (Boyle et al, 2017;Minor et al, 2014), one in-frame deletion including exon 13 of RAD21, one splice donor mutation (Ansari et al, 2014) and deletions spanning whole RAD21 (Deardorff et al, 2012;Pereza et al, 2015). Deardorff et al has also highlighted two previously published patients, with deletions spanning RAD21, diagnosed with Langer-Giedion syndrome but with clinical symptoms overlapping CdLS type 4 (McBrien et al, 2008;Wuyts et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 – Review of the literature

Gudmundsson

Annerén

Marcos‐Alcalde

et al. 2019

European Journal of Medical Genetics

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Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder where 70% of clinically diagnosed patients harbor a variant in one of five CdLS associated cohesin proteins. Around 500 variants have been identified to cause CdLS, however only eight different alterations have been identified in the RAD21 gene, encoding the RAD21 cohesin complex component protein that constitute the link between SMC1A and SMC3 within the cohesin ring. We report a 15-month-old boy presenting with developmental delay, distinct CdLS-like facial features, gastrointestinal reflux in early infancy, testis retention, prominent digit pads and diaphragmatic hernia. Exome sequencing revealed a novel RAD21 variant, c.1774_1776del, p.(Gln592del), suggestive of CdLS type 4. Segregation analysis of the two healthy parents confirmed the variant as de novo and bioinformatic analysis predicted the variant as disease-causing. Assessment by in silico structural model predicted that the p.Gln592del variant results in a discontinued contact between RAD21-Lys591 and the SMC1A residues Glu1191 and Glu1192, causing changes in the RAD21-SMC1A interface. In conclusion, we report a patient that expands the clinical description of CdLS type 4 and presents with a novel RAD21 p.(Glu592del) variant that causes a disturbed RAD21-SMC1A interface according to in silco structural modeling.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 – Review of the literature

Gudmundsson

Annerén

Marcos‐Alcalde

et al. 2019

European Journal of Medical Genetics

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“…Recently, Pereza et al wrote a letter to the editor of American Journal of Medical Genetics suggesting a revision of the diagnosis of their patient, originally diagnosed as LGS, suggesting that CdLS type 4 could be a more accurate diagnosis because the deleted fragment included RAD21 and 30 other RefSEq genes. 14 We propose a mixed LGS-CdLS type 4 phenotype as a better alternative term to describe the phenotype of our patient.…”

Section: Discussionmentioning

confidence: 99%

Mixed Phenotype of Langer–Giedion's and Cornelia de Lange's Syndromes in an 8q23.3-q24.1 Microdeletion without TRPS1 Deletion

et al. 2019

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Langer–Giedion's syndrome (LGS) or trichorhinophalangeal syndrome type II (TRPS II; MIM:150230) is a contiguous gene deletion syndrome caused by the haploinsufficiency of the TRPS1 and EXT1 genes. Cornelia de Lange's syndrome (CdLS) is a genetically heterogeneous dysmorphic syndrome where heterozygous mutations of RAD21 gene have been associated with a mild clinical presentation (CDLS type 4; MIM: 614701). We report a female patient with a 2.3-Mb interstitial deletion at 8q23.3-q24.1 encompassing EXT1 and RAD21 genes but not TRPS1. Clinical findings in this patient are correlated with a mixed phenotype of LGS and CdLS type 4.

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“…At first, in 2012, the patient had been diagnosed a Langer-Giedion syndrome [5]. After the advancements made in molecular and genetic diagnostics in the Republic of Croatia, in 2015, she was diagnosed with CdLS [6].…”

Section: Case Reportmentioning

confidence: 99%

A Thirteen-Year-Old Girl with Cornelia de Lange Syndrome – The First Case Described in Litigation

Lalić

2020

Open Access Maced J Med Sci

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AIM: The aim of this paper is to accentuate importance of the expert witness role, occupational medicine specialist, in litigation. The OM specialist proved his importance in broad spectrum of administrative court proceedings, assessment of working capacity, and different type of claims. CASE REPORT: Here is presented a case of a 13-year-old girl suffering Cornelia de Langue syndrome. The occupational medicine specialist concludes that the girl’s claim toward the Ministry of Demography, Family and Social Affairs is legitimate. Expert witness representing the above ministry came to conclusion that the patient is not heavily disabled due to her mobility and regular school attendance. Due to hearing aid her hearing is satisfactory and she is capable of dressing and feeding herself. In 2012, the girl was diagnosed with Langer-Giedion syndrome 8q23.3-q24.13 deletions and due to the development of molecular diagnosis only in 2015 RAD 21 gene deletion was discovered and she was correctly diagnosed. On examination, occupational medicine specialist found the patient suffering heavy deformations of locomotor system, small hands and feet, genua valga, and flat feet. The hearing is severely impaired in right and moderately in her left ear. Her mother states that she stopped soiling bed at the age of 8 and at present when going to toilette during night she becomes disoriented, sleeps badly, and screams. In the morning, she is not capable of preparing her own food. The patient needs to be examined by endocrinologist, her body is covered in exostoses and she heavily depends on other people. CONCLUSION: The patient is heavily disabled and in need of help for essential functioning at least until completion of secondary education.

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Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: Comments on the article by Pereza et al. [2012]

Cited by 8 publications

References 7 publications

A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 – Review of the literature

A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 – Review of the literature

Mixed Phenotype of Langer–Giedion's and Cornelia de Lange's Syndromes in an 8q23.3-q24.1 Microdeletion without TRPS1 Deletion

A Thirteen-Year-Old Girl with Cornelia de Lange Syndrome – The First Case Described in Litigation

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