Document Detail


Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures.
MedLine Citation:
PMID:  19904302     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microdeletion of chromosome 2q23.1 results in a novel syndrome previously reported in five individuals. Many of the del(2)(q23.1) cases were thought to have other syndromes such as Angelman, Prader-Willi, or Smith-Magenis because of certain overlapping clinical features. We report two new cases of the 2q23.1 microdeletion syndrome, describe the syndrome phenotype, define the minimal critical region, and analyze the expression of critical region genes toward identification of the causative gene(s) for the disorder. Individuals with del(2)(q23.1) have severe developmental and cognitive delays, minimal speech, seizures, microcephaly, mild craniofacial dysmorphism, behavioral disorders, and short stature. The deletions encompassing 2q23.1 range from >4 Mb to <200 kb, as identified by oligonucleotide and BAC whole-genome array comparative hybridization. The minimal critical region includes a single gene, MBD5, deleted in all cases, whereas all but one case also include deletion of EPC2. Quantitative real-time PCR of patient lymphoblasts/lymphocytes showed an approximately 50% reduced expression of MBD5 and EPC2 compared with controls. With similar phenotypes among the 2q23.1 deletion patients, the idea of one or more common genes causing the pathological defect seen in these patients becomes evident. As all five previous cases and the two cases in this report share one common gene, MBD5, we strongly suspect that haploinsufficiency of MBD5 causes most of the features observed in this syndrome.
Authors:
Stephen R Williams; Sureni V Mullegama; Jill A Rosenfeld; Aditi I Dagli; Eli Hatchwell; William P Allen; Charles A Williams; Sarah H Elsea
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-11
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  18     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-18     Completed Date:  2010-06-29     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  436-41     Citation Subset:  IM    
Affiliation:
Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 2 / genetics
Comparative Genomic Hybridization
DNA-Binding Proteins / genetics*
Female
Haplotypes*
Humans
In Situ Hybridization, Fluorescence
Intellectual Disability / genetics*,  pathology
Male
Microcephaly / genetics*,  pathology
Oligonucleotide Array Sequence Analysis
Prognosis
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Seizures / genetics*,  pathology
Speech Disorders / genetics*,  pathology
Syndrome
Young Adult
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/MBD5 protein, human; 0/RNA, Messenger
Comments/Corrections

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