Published online November 6, 2006
PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1687-e1695 (doi:10.1542/peds.2006-0395)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Friez, M. J.
Right arrow Articles by Stevenson, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friez, M. J.
Right arrow Articles by Stevenson, R. E.
Related Collections
Right arrow Genetics & Dysmorphology

ARTICLE

Recurrent Infections, Hypotonia, and Mental Retardation Caused by Duplication of MECP2 and Adjacent Region in Xq28

Michael J. Friez, PhDa, Julie R. Jones, PhDa, Katie Clarkson, MDa, Herbert Lubs, MDa, Dianne Abuelo, MDb, Jo-Ann Blaymore Bier, MDc, Shashidhar Pai, MDd, Richard Simensen, PhDa, Charles Williams, MDe, Philip F. Giampietro, MD, PhDf, Charles E. Schwartz, PhDa and Roger E. Stevenson, MDa

a Greenwood Genetic Center, Greenwood, South Carolina
b Department of Pediatrics, Rhode Island Hospital, Providence, Rhode Island
c Department of General Pediatrics, Children’s Hospital, Boston, Massachusetts
d Medical University of South Carolina, Charleston, South Carolina
e College of Medicine, University of Florida, Gainesville, Florida
f Marshfield Clinic, Medical Genetic Services, Marshfield, Wisconsin

OBJECTIVE. Our goal was to describe the neurologic and clinical features of affected males from families with X-linked patterns of severe mental retardation, hypotonia, recurrent respiratory infection, and microduplication of Xq28 that consistently includes the MECP2 (methyl-CpG binding protein 2) gene.

STUDY DESIGN. To identify duplications, multiplex ligation-dependent probe amplification of the MECP2 gene was performed on male probands from families with X-linked mental retardation. The males either had linkage to Xq28 or had a phenotype consistent with previous reports involving Xq28 functional disomy. After detection of a duplication of MECP2, additional family members were tested to confirm the MECP2 duplication segregated with the affected phenotype, and X-inactivation studies were performed on carrier females.

RESULTS. Six families with multiple affected males having MECP2 duplications were identified by multiplex ligation-dependent probe amplification, and the carrier mothers were subsequently shown to have highly skewed X inactivation. In 5 of 6 families, the microduplication extended proximally to include the L1 cell adhesion molecule gene. The primary clinical features associated with this microduplication are infantile hypotonia, recurrent respiratory infection, severe mental retardation, absence of speech development, seizures, and spasticity.

CONCLUSIONS. Although many of the phenotypic features of our patients are rather nonspecific in cohorts of individuals with syndromic and nonsyndromic mental retardation, the proneness to infection is quite striking because the patients had normal growth and were not physically debilitated. Although the etiology of the infections is not understood, we recommend considering MECP2 dosage studies and a genetics referral in individuals with severe developmental delay and neurologic findings, especially when a history of recurrent respiratory ailments has been documented.

Key Words: mental retardation • hypotonia • recurrent infection • MECP2 • duplication

Abbreviations: MECP2—methyl-CpG binding protein 2 gene • XLMR—X-linked mental retardation • L1CAM—L1 cell adhesion molecule gene • MLPA—multiplex ligation-dependent probe amplification • PCR—polymerase chain reaction • Ig—immunoglobulin • ANA—antinuclear antibody • CF—cystic fibrosis

Accepted Jun 9, 2006.




This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
R. C. Samaco, J. D. Fryer, J. Ren, S. Fyffe, H.-T. Chao, Y. Sun, J. J. Greer, H. Y. Zoghbi, and J. L. Neul
A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome
Hum. Mol. Genet., June 15, 2008; 17(12): 1718 - 1727.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
M. Bauters, H. Van Esch, M. J. Friez, O. Boespflug-Tanguy, M. Zenker, A. M. Vianna-Morgante, C. Rosenberg, J. Ignatius, M. Raynaud, K. Hollanders, et al.
Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair
Genome Res., June 1, 2008; 18(6): 847 - 858.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
A. K. Percy
Rett Syndrome: Recent Research Progress
J Child Neurol, May 1, 2008; 23(5): 543 - 549.
[Abstract] [PDF]

Home page
 J. Med. Genet.Home page
L. Villard
MECP2 mutations in males
J. Med. Genet., July 1, 2007; 44(7): 417 - 423.
[Abstract] [Full Text] [PDF]