Intergenerational and intrafamilial phenotypic variability in 22q11.2 Deletion syndrome subjects

BMC Medical Genetics

Claudio Pignata⁷  Maria Cristina Digilio^1,10  Paolo Rossi^1,12  Caterina Cancrini^1,12  Annarosa Soresina⁴  Gioacchino Scarano⁸  Alessandro Plebani⁴  Cristina Molinatto³  Baldassarre Martire^1,13  Silvana Martino³  Rita Consolini⁶  Maria Pia Cicalese²  Fabio Cardinale⁹  Rosa Bacchetta^1,11  Chiara Azzari¹  Pamela Puliafito^1,12  Vera Gallo⁵  Giuliana Giardino⁵  Emilia Cirillo⁵ 

[1] Department of Pediatrics, Anna Meyer Children’s University Hospital, Florence, Italy;Pediatric ImmunoHematology IRCCS, San Raffaele Hospital, Milan, Italy;Department of Pediatrics, University of Turin, Turin, Italy;A. Nocivelli Institute for Molecular Medicine, Pediatric Clinic, University of Brescia, Brescia, Italy;Department of Translational Medicine, “Federico II” University, Naples, Italy;Department of Internal and Experimental Medicine, University of Pisa, Pisa, Italy;Department of Translational Medical Sciences, Unit of Pediatric Immunology, “Federico II” University, via S. Pansini, 5-80131 Naples, Italy;Medical Genetics Unit, General Hospital G. Rummo, Benevento, Italy;Department of Pediatrics, Giovanni XXIII Pediatric Hospital, Bari, Italy;Medical Genetics, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy;San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan; Pediatric ImmunoHematology IRCCS San Raffaele Hospital, Milan, Italy;Department of Pediatrics, (DPUO), University of Rome Tor Vergata, Rome, Italy;Department of Biomedicine and Evolutive Aging, University of Bari, Bari, Italy

关键词: Phenotypic variability;    Immunodeficiency;    DiGeorge syndrome;    22q11.2 deletion syndrome;   

Others  :  1122550
DOI  :  10.1186/1471-2350-15-1

 received in 2013-07-17, accepted in 2013-12-27,  发布年份 2014

【 摘 要 】

Background

22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion syndrome, which occurs in approximately 1:4000 births. Familial autosomal dominant recurrence of the syndrome is detected in about 8-28% of the cases. Aim of this study is to evaluate the intergenerational and intrafamilial phenotypic variability in a cohort of familial cases carrying a 22q11.2 deletion.

Methods

Thirty-two 22q11.2DS subjects among 26 families were enrolled.

Results

Second generation subjects showed a significantly higher number of features than their transmitting parents (212 vs 129, P = 0.0015). Congenital heart defect, calcium-phosphorus metabolism abnormalities, developmental and speech delay were more represented in the second generation (P < 0.05). Ocular disorders were more frequent in the parent group. No significant difference was observed for the other clinical variables. Intrafamilial phenotypic heterogeneity was identified in the pedigrees. In 23/32 families, a higher number of features were found in individuals from the second generation and a more severe phenotype was observed in almost all of them, indicating the worsening of the phenotype over generations. Both genetic and epigenetic mechanisms may be involved in the phenotypic variability.

Conclusions

Second generation subjects showed a more complex phenotype in comparison to those from the first generation. Both ascertainment bias related to patient selection or to the low rate of reproductive fitness of adults with a more severe phenotype, and several not well defined molecular mechanism, could explain intergenerational and intrafamilial phenotypic variability in this syndrome.

【 授权许可】

   
2014 Cirillo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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