Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies

Iannicelli, Miriam, Brancati, Francesco, Mougou-Zerelli, Soumaya, Mazzotta, Annalisa, Thomas, Sophie, Elkhartoufi, Nadia, Travaglini, Lorena, Gomes, Céline, Ardissino, Gian Luigi, Bertini, Enrico, Boltshauser, Eugen, Castorina, Pierangela, D’Arrigo, Stefano, Fischetto, Rita, Leroy, Brigitte, Loget, Philippe, Bonnière, Maryse, Starck, Lena, Tantau, Julia, Gentilin, Barbara, Majore, Silvia, Swistun, Dominika, Flori, Elizabeth, Lalatta, Faustina, Pantaleoni, Chiara, Penzien, Johannes, Grammatico, Paola, The International JSRD Study Group, Gleeson, Joseph G., Dallapiccola, Bruno, Attie-Bitach, Tania, Valente, Enza Maria and Zankl, Andreas (2010) Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies. Human Mutation, 31 5: E1319-E1331. doi:10.1002/humu.21239

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Author Iannicelli, Miriam
Brancati, Francesco
Mougou-Zerelli, Soumaya
Mazzotta, Annalisa
Thomas, Sophie
Elkhartoufi, Nadia
Travaglini, Lorena
Gomes, Céline
Ardissino, Gian Luigi
Bertini, Enrico
Boltshauser, Eugen
Castorina, Pierangela
D’Arrigo, Stefano
Fischetto, Rita
Leroy, Brigitte
Loget, Philippe
Bonnière, Maryse
Starck, Lena
Tantau, Julia
Gentilin, Barbara
Majore, Silvia
Swistun, Dominika
Flori, Elizabeth
Lalatta, Faustina
Pantaleoni, Chiara
Penzien, Johannes
Grammatico, Paola
The International JSRD Study Group
Gleeson, Joseph G.
Dallapiccola, Bruno
Attie-Bitach, Tania
Valente, Enza Maria
Zankl, Andreas
Title Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies
Formatted title
Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies
Journal name Human Mutation   Check publisher's open access policy
ISSN 1059-7794
Publication date 2010-05-01
Sub-type Article (original research)
DOI 10.1002/humu.21239
Volume 31
Issue 5
Start page E1319
End page E1331
Total pages 13
Editor Richard G. H. Cotton
Garry R. Cutting
Place of publication Hoboken, NJ, U.S.A.
Publisher John Wiley & Sons
Language eng
Formatted abstract
Human ciliopathies are hereditary conditions caused by defects of proteins expressed at the primary cilium. Among ciliopathies, Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS) and nephronophthisis (NPH) present clinical and genetic overlap, being allelic at several loci. One of the most interesting gene is TMEM67, encoding the transmembrane protein meckelin. We performed mutation analysis of TMEM67 in 341 probands, including 265 JSRD representative of all clinical subgroups and 76 MKS fetuses. We identified 33 distinct mutations, of which 20 were novel, in 8/10 (80%) JS with liver involvement (COACH phenotype) and 12/76 (16%) MKS fetuses. No mutations were found in other JSRD subtypes, confirming the strong association between TMEM67 mutations and liver involvement. Literature review of all published TMEM67mutated cases was performed to delineate genotype-phenotype correlates. In particular, comparison of the types of mutations and their distribution along the gene in lethal versus non lethal phenotypes showed in MKS patients a significant enrichment of missense mutations falling in TMEM67 exons 8 to 15, especially when in combination with a truncating mutation. These exons encode for a region of unknown function in the extracellular domain of meckelin.
© 2010 Wiley-Liss, Inc.
Keyword TMEM67
Joubert syndrome
Meckel syndrome
Congenital hepatic fibrosis
COACH syndrome
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Created: Fri, 25 Feb 2011, 23:39:34 EST by Melanie Thomas on behalf of School of Medicine