Application of exome sequencing to diagnose a novel presentation of the Cornelia de Lange syndrome in an Afro-Caribbean family.
Caribbean
Cornelia de Lange syndrome
exome sequencing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
02
05
2020
accepted:
07
05
2020
pubmed:
9
6
2020
medline:
11
5
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Cornelia de Lange syndrome (CdLS) comprises a recognizable pattern of multiple congenital anomalies caused by variants of the DNA cohesion complex. Affected individuals may display a wide range of phenotypic severity, even within the same family. Exome sequencing and confirmatory Sanger sequencing showed the same previously described p.Arg629Ter NIPBL variant in two half-brothers affected with CdLS. Clinical evaluations were obtained in a pro bono genetics clinic. One brother had relatively mild proportionate limb shortening; the other had complete bilateral hypogenesis of the upper arm with absence of lower arm structures, terminal transverse defects, and no digit remnants. His complex lower limb presentation included long bone deficiency and a deviated left foot. The mother had intellectual disability and microcephaly but lacked facial features diagnostic of the CdLS. We describe a collaboration between a pediatrics team from a resource-limited nation and USA-based medical geneticists. Reports describing individuals of West Indian ancestry are rarely found in the medical literature. Here, we present a family of Afro-Caribbean ancestry with CdLS presenting with phenotypic variability, including unusual lower limb abnormalities. The observation of this novel family adds to our knowledge of the phenotypic and molecular aspects of CdLS.
Sections du résumé
BACKGROUND
Cornelia de Lange syndrome (CdLS) comprises a recognizable pattern of multiple congenital anomalies caused by variants of the DNA cohesion complex. Affected individuals may display a wide range of phenotypic severity, even within the same family.
METHODS
Exome sequencing and confirmatory Sanger sequencing showed the same previously described p.Arg629Ter NIPBL variant in two half-brothers affected with CdLS. Clinical evaluations were obtained in a pro bono genetics clinic.
RESULTS
One brother had relatively mild proportionate limb shortening; the other had complete bilateral hypogenesis of the upper arm with absence of lower arm structures, terminal transverse defects, and no digit remnants. His complex lower limb presentation included long bone deficiency and a deviated left foot. The mother had intellectual disability and microcephaly but lacked facial features diagnostic of the CdLS.
CONCLUSION
We describe a collaboration between a pediatrics team from a resource-limited nation and USA-based medical geneticists. Reports describing individuals of West Indian ancestry are rarely found in the medical literature. Here, we present a family of Afro-Caribbean ancestry with CdLS presenting with phenotypic variability, including unusual lower limb abnormalities. The observation of this novel family adds to our knowledge of the phenotypic and molecular aspects of CdLS.
Identifiants
pubmed: 32511891
doi: 10.1002/mgg3.1318
pmc: PMC7434751
doi:
Substances chimiques
Cell Cycle Proteins
0
NIPBL protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1318Subventions
Organisme : NICHD NIH HHS
ID : P50 HD105354
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Am J Med Genet A. 2012 Jun;158A(6):1481-5
pubmed: 22581668
Mol Genet Genomic Med. 2020 Aug;8(8):e1318
pubmed: 32511891
Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):198-205
pubmed: 27164022
Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):146-54
pubmed: 27120109
Clin Genet. 2016 May;89(5):584-9
pubmed: 26701315
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Nature. 2012 Sep 13;489(7415):313-7
pubmed: 22885700
Fly (Austin). 2012 Apr-Jun;6(2):80-92
pubmed: 22728672
Rev Panam Salud Publica. 2015 Nov;38(5):425-30
pubmed: 26837529
Hum Mutat. 2013 Dec;34(12):1589-96
pubmed: 24038889
Am J Med Genet A. 2007 Jun 15;143A(12):1287-96
pubmed: 17508425
Am J Hum Genet. 2012 Jun 8;90(6):1014-27
pubmed: 22633399
Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):155-62
pubmed: 27120260
Am J Med Genet Suppl. 1986;2:215-38
pubmed: 3146293
Am J Hum Genet. 2007 Mar;80(3):485-94
pubmed: 17273969
Annu Rev Genomics Hum Genet. 2008;9:303-20
pubmed: 18767966
Am J Med Genet A. 2005 May 15;135(1):103-5
pubmed: 15723327
J Med Genet. 2013 May;50(5):339-44
pubmed: 23505322
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Am J Med Genet A. 2019 Feb;179(2):150-158
pubmed: 30614194
Nat Genet. 2004 Jun;36(6):631-5
pubmed: 15146186