MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies. Journal of Human Genetics (2011) 56, 508-515; doi: 10.1038/jhg.2011.50; published online 19 May 2011

Artuso, R., Papa, F.T., Grillo, E., Mucciolo, M., Yasui, D.H., Dunaway, K.W., et al. (2011). Investigation of modifier genes within copy number variations in Rett syndrome. JOURNAL OF HUMAN GENETICS, 56(7), 508-515 [10.1038/jhg.2011.50].

Investigation of modifier genes within copy number variations in Rett syndrome

PAPA F. T.;DISCIGLIO V.;MARI F.;RENIERI A.;ARIANI F.
2011-01-01

Abstract

MECP2 mutations are responsible for two different phenotypes in females, classical Rett syndrome and the milder Zappella variant (Z-RTT). We investigated whether copy number variants (CNVs) may modulate the phenotype by comparison of array-CGH data from two discordant pairs of sisters and four additional discordant pairs of unrelated girls matched by mutation type. We also searched for potential MeCP2 targets within CNVs by chromatin immunopreceipitation microarray (ChIP-chip) analysis. We did not identify one major common gene/region, suggesting that modifiers may be complex and variable between cases. However, we detected CNVs correlating with disease severity that contain candidate modifiers. CROCC (1p36.13) is a potential MeCP2 target, in which a duplication in a Z-RTT and a deletion in a classic patient were observed. CROCC encodes a structural component of ciliary motility that is required for correct brain development. CFHR1 and CFHR3, on 1q31.3, may be involved in the regulation of complement during synapse elimination, and were found to be deleted in a Z-RTT but duplicated in two classic patients. The duplication of 10q11.22, present in two Z-RTT patients, includes GPRIN2, a regulator of neurite outgrowth and PPYR1, involved in energy homeostasis. Functional analyses are necessary to confirm candidates and to define targets for future therapies. Journal of Human Genetics (2011) 56, 508-515; doi: 10.1038/jhg.2011.50; published online 19 May 2011
2011
Artuso, R., Papa, F.T., Grillo, E., Mucciolo, M., Yasui, D.H., Dunaway, K.W., et al. (2011). Investigation of modifier genes within copy number variations in Rett syndrome. JOURNAL OF HUMAN GENETICS, 56(7), 508-515 [10.1038/jhg.2011.50].
File in questo prodotto:
File Dimensione Formato  
Artuso R et al. 2011 J Hum Genet.pdf

non disponibili

Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 558.62 kB
Formato Adobe PDF
558.62 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/18959