Cornelia de Lange综合征患者临床特征及其遗传学分析2例报告及文献复习

doi:10.13481/j.1671-587X.20250225

Abstract

Abstract:

Cornelia de Lange syndrome is a rare congenital malformation disease， and its typical features include growth restriction， mental retardation， craniofacial abnormality and hirsutism. This study reported 2 cases of CdLS patients， summarized their clinical manifestations and gene mutation characteristics， and the relevant literatures were reviewed. Patient 1， a 5-year-old girl， was admitted to the hospital due to growth retardation. Physical examination revealed hirsutism， monobrow， small and sparse teeth， hemangiomas （approximately 2 cm×2 cm） on the chest and back， delayed language development， and intellectual disability. The height was 98 cm ［≤-2 standard deviation（SD）］， the weight was 15 kg （-2SD--1SD）， the head circumference was 46 cm （-3SD--2SD）. Brain magnetic resonance imaging（MRI） plain scan showed slightly enlarged left lateral ventricle and bilateral lateral ventricle triangles， slightly thickened bilateral maxillary sinus and ethmoid sinus mucosa. Echocardiography revealed mild regurgitation of the mitral and tricuspid valves. Patient 2， a 1-month-old girl， was admitted to the hospital due to postpartum shortness of breath. The physical examination highlighted hirsutism， short nose， soft cleft palate， dysphagia， positive three-concave sign， audible throat sound， small hands， palm penetration in the left hand， short fifth finger of the right hand， limited right hip abduction， foot varus， and a white spot at the bottom of the right eye. Ultrasonography at 1 month showed mild regurgitation of the tricuspid valve and an open foramen ovale. Brain MRI at 2 d showed a few patchy low-signal shadows in the longitudinal fissure cistern and tentorium， a small amount of subarachnoid hemorrhage， and a small amount of fluid in the bilateral maxillary sinus， ethmoid sinus， and middle ear mastoid. No obvious structural or numerical abnormalities were observed in the chromosome karyotypes. Whole-exome sequencing detected a heterozygous variation of c.6653_6655del in the NIPBL gene in patient 1 and a heterozygous variation of c.337C>T in the NIPBL gene in patient 2. These variations were not found in their parents. The study revealed that NIPBL gene variation could be the genetic cause of the two patients with CdLS. The identification of the variation c.337C>T may expand the variation spectrum of the NIPBL gene， providing valuable insights into the pathogenic genetic basis of CdLS.

Key words: Cornelia de Lange syndrome, NIPBL gene, Gene variation, Variation spectrum

CLC Number:

R725.9

Meijiao CAI,Jiayan CHEN,Xiaomin MA,Yanru HUANG,Jian ZHANG,Yunsheng GE. Clinical characteristics and genetic analysis of patients with Cornelia de Lange syndrome: A report of 2 cases and literature review[J].Journal of Jilin University(Medicine Edition), 2025, 51(2): 501-507.

Figures/Tables 2

References 24

1	SZYCA R， LEKSOWSKI K. Cornelia de Lange syndrome-characteristics and laparoscopic treatment modalities of reflux based on own material［J］. Wideochir Inne Tech Maloinwazyjne， 2011， 6（3）： 173-177.
2	OPITZ J M. The brachmann-de Lange syndrome［J］. Am J Med Genet， 1985， 22（1）： 89-102.
3	BARISIC I， TOKIC V， LOANE M， et al. Descriptive epidemiology of Cornelia de Lange syndrome in Europe［J］. Am J Med Genet A， 2008， 146A（1）： 51-59.
4	MEI L B， LIANG D S， HUANG Y R， et al. Two novel NIPBL gene mutations in Chinese patients with Cornelia de Lange syndrome［J］. Gene， 2015， 555（2）： 476-480.
5	SAROGNI P， PALLOTTA M M， MUSIO A. Cornelia de Lange syndrome： from molecular diagnosis to therapeutic approach［J］. J Med Genet， 2020， 57（5）： 289-295.
6	KLINE A D， MOSS J F， SELICORNI A， et al. Diagnosis and management of Cornelia de Lange syndrome： first international consensus statement ［J］. Nat Rev Genet， 2018， 19（10）： 649-666.
7	ALONSO-GIL D， LOSADA A. NIPBL and cohesin： new take on a classic tale［J］. Trends Cell Biol， 2023， 33（10）： 860-871.
8	MUSIO A， SELICORNI A， FOCARELLI M L， et al. X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations［J］. Nat Genet， 2006， 38（5）： 528-530.
9	INFANTE E， ALKORTA-ARANBURU G， EL-GHARBAWY A. Rare form of autosomal dominant familial Cornelia de Lange syndrome due to a novel duplication in SMC3 ［J］. Clin Case Rep， 2017， 5（8）： 1277-1283.
10	KRAB L C， MARCOS-ALCALDE I， ASSAF M， et al. Delineation of phenotypes and genotypes related to cohesin structural protein RAD21［J］. Hum Genet， 2020， 139（5）： 575-592.
11	LI Z L， LIU C， XIN H M， et al. Establishment of a transgene-free iPS cell line （SDQLCHi046-A） from a young patient bearing a HDAC8 mutation and suffering from Cornelia de Lange Syndrome［J］. Stem Cell Res， 2023， 66： 102984.
12	OLLEY G， ANSARI M， BENGANI H， et al. BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome［J］. Nat Genet， 2018， 50（3）： 329-332.
13	KUZNIACKA A， WIERZBA J， RATAJSKA M， et al. Spectrum of NIPBL gene mutations in Polish patients with Cornelia de Lange syndrome［J］. J Appl Genet， 2013， 54（1）： 27-33.
14	MOSS J， PENHALLOW J， ANSARI M， et al. Genotype-phenotype correlations in Cornelia de Lange syndrome： behavioral characteristics and changes with age［J］. Am J Med Genet A， 2017， 173（6）： 1566-1574.
15	周平，朱琳，范琼丽，等. Cornelia de Lange综合征首个国际共识的解读［J］. 中国当代儿科杂志， 2020， 22（8）： 815-820.
16	GUTIERREZ-ESCRIBANO P， NEWTON M D， LLAURÓ A， et al. A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules［J］. Sci Adv， 2019， 5（11）： eaay6804.
17	TONKIN E T， WANG T J， LISGO S， et al. NIPBL， encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B， is mutated in Cornelia de Lange syndrome［J］. Nat Genet， 2004， 36（6）： 636-641.
18	GAO D Y， ZHU B J， CAO X， et al. Roles of NIPBL in maintenance of genome stability［J］. Semin Cell Dev Biol， 2019， 90： 181-186.
19	WEISS F D， CALDERON L， WANG Y F， et al. Neuronal genes deregulated in Cornelia de Lange Syndrome respond to removal and re-expression of cohesin［J］. Nat Commun， 2021， 12（1）： 2919.
20	BERMUDEZ V P， FARINA A， HIGASHI T L， et al. In vitro loading of human cohesin on DNA by the human Scc2-Scc4 loader complex［J］. Proc Natl Acad Sci U S A， 2012， 109（24）： 9366-9371.
21	REMESEIRO S， CUADRADO A， KAWAUCHI S， et al. Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome［J］. Biochim Biophys Acta， 2013， 1832（12）： 2097-2102.
22	FOGLIA M， GUARRERA L， KUROSAKI M， et al. The NIPBL-gene mutation of a Cornelia de Lange Syndrome patient causes deficits in the hepatocyte differentiation of induced Pluripotent Stem Cells via altered chromatin-accessibility［J］. Cell Mol Life Sci， 2024， 81（1）： 439.
23	MANNINI L， CUCCO F， QUARANTOTTI V， et al. Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange syndrome［J］. Hum Mutat， 2013， 34（12）： 1589-1596.
24	KAUR M， BLAIR J， DEVKOTA B， et al. Genomic analyses in Cornelia de Lange syndrome and related diagnoses： novel candidate genes， genotype-phenotype correlations and common mechanisms［J］. Am J Med Genet A， 2023， 191（8）： 2113-2131.

Clinical characteristics and genetic analysis of patients with Cornelia de Lange syndrome: A report of 2 cases and literature review

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