Wolfram syndrome 1 in the Italian population: genotype-phenotype correlations

被引:30
作者
Rigoli, Luciana [1 ]
Aloi, Concetta [2 ]
Salina, Alessandro [2 ]
Di Bella, Chiara [1 ]
Salzano, Giuseppina [1 ]
Caruso, Rosario [1 ]
Mazzon, Emanuela [3 ]
Maghnie, Mohamad [4 ]
Patti, Giuseppa [4 ]
D'Annunzio, Giuseppe [5 ]
Lombardo, Fortunato [1 ]
机构
[1] Univ Messina, Dept Human Pathol, Messina, Italy
[2] Ist Giannina Gaslini, LABSIEM Lab Study Inborn Errors Metab, Genoa, Italy
[3] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
[4] Univ Genoa, Dept Pediat, Ist Giannina Gaslini, Genoa, Italy
[5] Ist Giannina Gaslini, Dept Pediat, Genoa, Italy
关键词
DIABETES-MELLITUS; OPTIC ATROPHY; WFS1; GENE; HOMOZYGOUS MUTATION; DEAFNESS DIDMOAD; PROTEIN; EXPRESSION; IDENTIFICATION; COMPLICATIONS; INSIPIDUS;
D O I
10.1038/s41390-019-0487-4
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Objectives We studied 45 patients with Wolfram syndrome 1 (WS1) to describe their clinical history and to search for possible genotype-phenotype correlations. Methods Clinical criteria contributing to WS1 diagnosis were analyzed. The patients were classified into three genotypic classes according to type of detected mutations. Results WS1 prevalence in Italy is 0.74/1,000,000. All four manifestations of DIDMOAD were found in 46.7% of patients. Differently combined WS1 clinical features were detected in 53.3% of patients. We found 35 WFS1 different mutations and a novel missense mutation, c.1523A>G. WS1 patients were homozygotes or compound heterozygotes for WFS1 mutations except for 2 heterozygote patients (4.5%). Each genotypic group exhibited a different age onset of DM, D, and DI but not of OA. Genotypic Group 2 patients manifested a lower number of clinical manifestations compared to Groups 1 and 3. Moreover, genotypic Group 1 patients tended to have a shorter survival time than the other groups. No differences were found regarding type of clinical pictures. Conclusions Our study suggested that molecular WFS1 typing is a useful tool for early assessment of clinical history, follow-up, and prognosis of WS1.
引用
收藏
页码:456 / 462
页数:7
相关论文
共 40 条
[1]   Bleeding tendency in Wolfram syndrome: a newly identified feature with phenotype genotype correlation [J].
Al-Sheyyab, M ;
Jarrah, N ;
Younis, E ;
Shennak, MM ;
Hadidi, A ;
Awidi, A ;
El-Shanti, H ;
Ajlouni, K .
EUROPEAN JOURNAL OF PEDIATRICS, 2001, 160 (04) :243-246
[2]   Wolfram Syndrome: New Mutations, Different Phenotype [J].
Aloi, Concetta ;
Salina, Alessandro ;
Pasquali, Lorenzo ;
Lugani, Francesca ;
Perri, Katia ;
Russo, Chiara ;
Tallone, Ramona ;
Ghiggeri, Gian Marco ;
Lorini, Renata ;
d'Annunzio, Giuseppe .
PLOS ONE, 2012, 7 (01)
[3]   A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2 [J].
Amr, Sami ;
Heisey, Cindy ;
Zhang, Min ;
Xia, Xia-Juan ;
Shows, Kathryn H. ;
Ajlouni, Kamel ;
Pandya, Arti ;
Satin, Leslie S. ;
El-Shanti, Hatem ;
Shiang, Rita .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (04) :673-683
[4]   NEURODEGENERATION AND DIABETES - UK NATIONWIDE STUDY OF WOLFRAM (DIDMOAD) SYNDROME [J].
BARRETT, TG ;
BUNDEY, SE ;
MACLEOD, AF .
LANCET, 1995, 346 (8988) :1458-1463
[5]   Microvascular diabetes complications in wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]) -: An age- and duration-matched comparison with common type 1 diabetes [J].
Cano, Aline ;
Molines, Laurent ;
Valero, Rene ;
Simonin, Gilbert ;
Paquis-Flucklinger, Veronique ;
Vialettes, Bernard ;
Azoulay, J. P. ;
Bihan, H. ;
Blickle, J. F. ;
Bonneau, D. ;
Bougneres, P. ;
Brassart, J. P. ;
Chabas, D. ;
Chabrol, B. ;
Chaillous, L. ;
Chanson, P. ;
Coutant, R. ;
Delobel, B. ;
Dollfus, H. ;
Dufaitre, L. ;
Francannet, C. ;
Huber, K. ;
Journel, H. ;
de Kerdanet, M. ;
Kitzis, A. ;
Lecomte, P. ;
Linglart, A. ;
Matthis, S. ;
Mesnage, V. ;
Mignot, B. ;
N'Guyen, K. ;
Odent, S. ;
Raccah, D. ;
Rouault, T. ;
Sadoul, J. L. ;
Sarda, P. ;
Siagudy, S. .
DIABETES CARE, 2007, 30 (09) :2327-2330
[6]   Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay [J].
Colosimo, A ;
Guida, V ;
Rigoli, L ;
Di Bella, C ;
De Luca, A ;
Briuglia, S ;
Stuppia, L ;
Salpietro, DC ;
Dallapiccola, B .
HUMAN MUTATION, 2003, 21 (06) :622-629
[7]   Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype [J].
de Heredia, Miguel Lopez ;
Cleries, Ramon ;
Nunes, Virginia .
GENETICS IN MEDICINE, 2013, 15 (07) :497-506
[8]   Wolfram syndrome: MAMs' connection? [J].
Delprat, Benjamin ;
Maurice, Tangui ;
Delettre, Cecile .
CELL DEATH & DISEASE, 2018, 9
[9]   Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families [J].
Domènech, E ;
Gómez-Zaera, M ;
Nunes, V .
CLINICAL GENETICS, 2004, 65 (06) :463-469
[10]   Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q [J].
El-Shanti, H ;
Lidral, AC ;
Jarrah, N ;
Druhan, L ;
Ajlouni, K .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (04) :1229-1236