A versatile one-pot nitro-Mannich/lactamization cascade for the direct synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones has been developed. The reaction is easy to perform and broad in scope, and high levels of diastereoselectivity can be achieved

Alessandra Ferlini

Chiara Scotton

Chongyi Jiang

Claudio Campa

Davide Ognibene

Dieter Bosshardt

Domenica Taruscio

Francesca Gualandi

Francesco Brancati

Jianguo Zhang

Leonardo Trombelli

Marcella Neri

Marco Salvatore

Maria Chiara De Stefano

Maria Sofia Falzarano

Mingyan Fang

Paolo Perri

Patrizia Sabatelli

Rachele Rossi

Rita Selvatici

Roberto Farina

Stefania Bigoni

Frontiers in Genetics

Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations.</p

Stefania Bigoni (213916)

Marcella Neri (133019)

Chiara Scotton (133015)

Roberto Farina (6247529)

Patrizia Sabatelli (3131541)

Chongyi Jiang (6247532)

Jianguo Zhang (6482)

Maria Sofia Falzarano (133021)

Rachele Rossi (2501005)

Davide Ognibene (6247535)

Rita Selvatici (6247538)

Francesca Gualandi (133032)

Dieter Bosshardt (627048)

Paolo Perri (845626)

Claudio Campa (6247541)

Francesco Brancati (294036)

Marco Salvatore (470253)

Maria Chiara De Stefano (6247544)

Domenica Taruscio (513206)

Leonardo Trombelli (6247547)

Mingyan Fang (6247550)

Alessandra Ferlini (133038)

FigShare

Table_1_Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family.docx

Only a few genes involved in teeth development and morphology are known to be responsible for tooth abnormalities in Mendelian-inherited diseases. We studied an inbred family of Pakistani origin in which two first-cousin born brothers are affected by early tooth loss with peculiar teeth abnormalities characterized by the absence of cementum formation. Whole exome sequencing revealed a H2665L homozygous sequence variant in the VCAN gene. Dominant splicing mutations in VCAN are known to cause Wagner syndrome or vitreoretinopathy. We explored teeth morphology in these two patients, while versican expression was assessed by western blot analysis. Early signs of vitreoretinopathy were found in the elder brother while the parents were completely negative. Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations

Bigoni, Stefania

Neri, Marcella

Scotton, Chiara

Farina, Roberto

Sabatelli, Patrizia

Jiang, Chongyi

Zhang, Jianguo

Falzarano, Maria Sofia

Rossi, Rachele

Ognibene, Davide

Selvatici, Rita

Gualandi, Francesca

Bosshardt, Dieter

Perri, Paolo

Campa, Claudio

Brancati, Francesco

Salvatore, Marco

De Stefano, Maria Chiara

Taruscio, Domenica

Trombelli, Leonardo

Fang, Mingyan

Ferlini, Alessandra

Archivio istituzionale della ricerca - Università di Ferrara

English

Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family

Bern Open Repository and Information System (BORIS)

Homozygous Recessive Versican Missense Variation Is Associated With Early Teeth Loss in a Pakistani Family.

Directory of Open Access Journals

Sophie M.-C. Pelletier (2136106)

Peter C. Ray (2136103)

Darren J. Dixon (1297407)