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Phenotypic Spectrum of Simpson– G olabi– B ehmel Syndrome in a Series of 42 Cases With a Mutation in GPC 3 and Review of the Literature
Author(s) -
COTTEREAU EDOUARD,
MORTEMOUSQUE ISABELLE,
MOIZARD MARIEPIERRE,
BÜRGLEN LYDIE,
LACOMBE DIDIER,
GILBERTDUSSARDIER BRIGITTE,
SIGAUDY SABINE,
BOUTE ODILE,
DAVID ALBERT,
FAIVRE LAURENCE,
AMIEL JEANNE,
ROBERTSON ROBERT,
VIANA RAMOS FABIANA,
BIETH ERIC,
ODENT SYLVIE,
DEMEER BÉNÉDICTE,
MATHIEU MICHÉLE,
GAILLARD DOMINIQUE,
VAN MALDERGEM LIONEL,
BAUJAT GENEVIÉVE,
MAYSTADT ISABELLE,
HÉRON DELPHINE,
VERLOES ALAIN,
PHILIP NICOLE,
CORMIERDAIRE VALÉRIE,
FROUTÉ MARIEFRANÇOISE,
PINSON LUCILE,
BLANCHET PATRICIA,
SARDA PIERRE,
WILLEMS MARJOLAINE,
JACQUINET ADELINE,
RATBI ILHAM,
VAN DEN ENDE JENNEKE,
LACKMYPORT LIS MARYLIN,
GOLDENBERG ALICE,
BONNEAU DOMINIQUE,
ROSSIGNOL SYLVIE,
TOUTAIN ANNICK
Publication year - 2013
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.31360
Subject(s) - macrocephaly , gigantism , organomegaly , gene duplication , mutation , genetics , genetic heterogeneity , genetic testing , intellectual disability , gene mutation , phenotype , medicine , biology , gene , pathology , disease
Simpson–Golabi–Behmel syndrome (SGBS) is a rare X‐linked multiple congenital abnormality/intellectual disability syndrome characterized by pre‐ and post‐natal overgrowth, distinctive craniofacial features, macrocephaly, variable congenital malformations, organomegaly, increased risk of tumor and mild/moderate intellectual deficiency. In 1996, Glypican 3 ( GPC3 ) was identified as the major gene causing SGBS but the mutation detection rate was only 28–70%, suggesting either genetic heterogeneity or that some patients could have alternative diagnoses. This was particularly suggested by some reports of atypical cases with more severe prognoses. In the family reported by Golabi and Rosen, a duplication of GPC4 was recently identified, suggesting that GPC4 could be the second gene for SGBS but no point mutations within GPC4 have yet been reported. In the genetics laboratory in Tours Hospital, GPC3 molecular testing over more than a decade has detected pathogenic mutations in only 8.7% of individuals with SGBS. In addition, GPC4 mutations have not been identified thus raising the question of frequent misdiagnosis. In order to better delineate the phenotypic spectrum of SGBS caused by GPC3 mutations, and to try to define specific clinical criteria for GPC3 molecular testing, we reviewed the clinical features of all male cases with a GPC3 mutation identified in the two molecular laboratories providing this test in France (Tours and Paris). We present here the results of the analysis of 42 patients belonging to 31 families and including five fetuses and three deceased neonates. © 2013 Wiley Periodicals, Inc.