Pubblicazione scientifica

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

FILONE TECNOLOGICO	TEMA
produzione e cattura	cattura selettiva sistemi di individuazione sottomarini (es. ecoscandaglio, ecc.)

RIASSUNTO

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.

DATA

Data di pubblicazione: 02/01/2014

AUTORI

CIRILLO EMILIA
GIARDINO GIULIANA
GALLO VERA
PULIAFITO PAMELA
AZZARI CHIARA
BACCHETTA ROSA
CARDINALE FABIO
CICALESE MARIA PIA
CONSOLINI RITA
MARTINO SILVANA
MARTIRE BALDASSARRE
MOLINATTO CRISTINA
PLEBANI ALESSANDRO
SCARANO GIOACCHINO
SORESINA ANNAROSA
CANCRINI CATERINA
ROSSI PAOLO
DIGILIO MARIA CRISTINA
PIGNATA CLAUDIO

ENTE DI AFFERENZA

Department of Translational Medicine “Federico II” University Naples Italy
Department of Pediatrics Anna Meyer Children’s University Hospital Florence Italy
Department of Translational Medical Sciences Unit of Pediatric Immunology “Federico II” University via S. Pansini 5-80131 Naples Italy
DEPT PEDIATRICS DPUO UNIV ROME TOR VERGATA ROME ITALY
SAN RAFFAELE TELETHON INST GENE THERAPY HSR TIGET MILAN PEDIATRIC IMMUNOHEMATOLOGY IRCCS SAN RAFFAELE HOSPITAL MILAN ITALY
DEPT PEDIATRICS GIOVANNI XXIII PEDIATRIC HOSPITAL BARI ITALY
PEDIATRIC IMMUNOHEMATOLOGY IRCCS SAN RAFFAELE HOSPITAL MILAN ITALY
DEPT INTERNAL & EXPERIMENTAL MEDICINE UNIV PISA PISA ITALY
DEPT PEDIATRICS UNIV TURIN TURIN ITALY
DEPT BIOMEDICINE & EVOLUTIVE AGING UNIV BARI BARI ITALY
A NOCIVELLI INST MOLECULAR MEDICINE PEDIATRIC CLINIC UNIV BRESCIA BRESCIA ITALY
MEDICAL GENETICS UNIT GEN HOSPITAL G RUMMO BENEVENTO ITALY
MEDICAL GENETICS BAMBINO GESU PEDIATRIC HOSPITAL IRCCS ROME ITALY

RIVISTA

BMC Medical Genetics, 15, 1

IMPACT FACTOR

1,780

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