Interstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620552
Title:
Interstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients.
Authors:
Osio, D.; Rankin, Julia; Koillinen, H.; Reynolds, A.; Van Esch, H.
Abstract:
Over the past decade chromosomal microarray analysis (array CGH) has allowed the discovery of many novel disease-causing recurrent microdeletion and microduplication syndromes. Here we present three unrelated patients (2F; 1M) from three different countries, with developmental delay, intellectual disability, hypotonia, fatigue, and highly similar dysmorphic facial features. Shared facial features are a broad and wide forehead, similar shape of the eyes with long palpebral fissures, a bulbous tip of the nose and thick lips. Intellectual disabilities range from mild to severe. One female patient and the male patient were investigated in childhood for significant hypotonia thought to be suggestive of a neuromuscular disorder. The two female patients also show excessive fatigue with daytime somnolence. The patients carry overlapping, de novo microdeletions of chromosome 17q11.2, with sizes ranging from 0.97 to 1.18 Mb. The smallest region of overlap (SRO) between the three patients is 863 kb, and contains seven genes, five of which are predicted to exhibit haploinsufficiency (CDK5R1, PSMD11, RHOT1, SUZ12, ZNF207) although none has yet been associated with genetic syndromes. Of these five genes, the brain expressed CDK5R1 gene constitutes a good candidate for the developmental delay, while the RHOT1 gene, involved in mitochondrial trafficking, might underlie the hypotonia and the excessive fatigue.
Citation:
Interstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients. 2017 Am. J. Med. Genet. A
Publisher:
Wiley
Journal:
American journal of medical genetics. Part A
Issue Date:
12-Nov-2017
URI:
http://hdl.handle.net/11287/620552
DOI:
10.1002/ajmg.a.38499
PubMed ID:
29130599
Additional Links:
http://dx.doi.org/10.1002/ajmg.a.38499
Type:
Journal Article
Language:
en
ISSN:
1552-4833
Appears in Collections:
Clinical Genetics (Peninsula Genetics); 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorOsio, D.en
dc.contributor.authorRankin, Juliaen
dc.contributor.authorKoillinen, H.en
dc.contributor.authorReynolds, A.en
dc.contributor.authorVan Esch, H.en
dc.date.accessioned2017-12-07T14:03:48Z-
dc.date.available2017-12-07T14:03:48Z-
dc.date.issued2017-11-12-
dc.identifier.citationInterstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients. 2017 Am. J. Med. Genet. Aen
dc.identifier.issn1552-4833-
dc.identifier.pmid29130599-
dc.identifier.doi10.1002/ajmg.a.38499-
dc.identifier.urihttp://hdl.handle.net/11287/620552-
dc.description.abstractOver the past decade chromosomal microarray analysis (array CGH) has allowed the discovery of many novel disease-causing recurrent microdeletion and microduplication syndromes. Here we present three unrelated patients (2F; 1M) from three different countries, with developmental delay, intellectual disability, hypotonia, fatigue, and highly similar dysmorphic facial features. Shared facial features are a broad and wide forehead, similar shape of the eyes with long palpebral fissures, a bulbous tip of the nose and thick lips. Intellectual disabilities range from mild to severe. One female patient and the male patient were investigated in childhood for significant hypotonia thought to be suggestive of a neuromuscular disorder. The two female patients also show excessive fatigue with daytime somnolence. The patients carry overlapping, de novo microdeletions of chromosome 17q11.2, with sizes ranging from 0.97 to 1.18 Mb. The smallest region of overlap (SRO) between the three patients is 863 kb, and contains seven genes, five of which are predicted to exhibit haploinsufficiency (CDK5R1, PSMD11, RHOT1, SUZ12, ZNF207) although none has yet been associated with genetic syndromes. Of these five genes, the brain expressed CDK5R1 gene constitutes a good candidate for the developmental delay, while the RHOT1 gene, involved in mitochondrial trafficking, might underlie the hypotonia and the excessive fatigue.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://dx.doi.org/10.1002/ajmg.a.38499en
dc.rightsArchived with thanks to American journal of medical genetics. Part Aen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleInterstitial microdeletion of 17q11.2 is associated with hypotonia, fatigue, intellectual disability, and a subtle facial phenotype in three unrelated patients.en
dc.typeJournal Articleen
dc.identifier.journalAmerican journal of medical genetics. Part Aen
dc.type.versionIn press (epub ahead of print)en

Related articles on PubMed

All Items in RD&E Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.