Exploring the Impact of Genetics in a Large Cohort of Moebius Patients by Trio Whole Exome Sequencing

被引:1
作者
Moresco, Giada [1 ]
Bedeschi, Maria Francesca [2 ]
Venturin, Marco [3 ]
Villa, Roberta [4 ]
Costanza, Jole [5 ,8 ]
Mauri, Alessia [5 ,9 ]
Santaniello, Carlo [5 ,10 ]
Picciolini, Odoardo [6 ]
Messina, Laura [6 ]
Triulzi, Fabio [7 ]
Miozzo, Monica Rosa [1 ,4 ]
Rondinone, Ornella [1 ]
Fontana, Laura [1 ,4 ]
机构
[1] Univ Milan, Dept Hlth Sci, Med Genet, I-20142 Milan, Italy
[2] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Med Genet Unit, I-20122 Milan, Italy
[3] Univ Milan, Dept Med Biotechnol & Translat Med, I-20054 Milan, Italy
[4] ASST Santi Paolo & Carlo, Med Genet Unit, I-20142 Milan, Italy
[5] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Res Labs Coordinat Unit, I-20122 Milan, Italy
[6] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Pediat Phys Med & Rehabil Unit, I-20122 Milan, Italy
[7] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Neuroradiol Unit, I-20122 Milan, Italy
[8] Nerviano Med Sci, Biol Dept, Viale Pasteur 10, I-20014 Milan, Italy
[9] Univ Milan, Pediat Clin Res Ctr Romeo & Enrica Invernizzi, Dept Biomed & Clin Sci, I-20157 Milan, Italy
[10] Ctr Diagnost Italiano, Lab Med Genet, I-20147 Milan, Italy
关键词
Moebius syndrome; WES; rare disease; cohort analysis; trio analysis; MOBIUS-SYNDROME; MUTATIONS; OPHTHALMOPLEGIA; CHROMOSOME-13; EXCLUSION;
D O I
10.3390/genes15080971
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Moebius syndrome (MBS) is a rare congenital disorder characterized by non-progressive facial palsy and ocular abduction paralysis. Most cases are sporadic, but also rare familial cases with autosomal dominant transmission and incomplete penetrance/variable expressivity have been described. The genetic etiology of MBS is still unclear: de novo pathogenic variants in REV3L and PLXND1 are reported in only a minority of cases, suggesting the involvement of additional causative genes. With the aim to uncover the molecular causative defect and identify a potential genetic basis of this condition, we performed trio-WES on a cohort of 37 MBS and MBS-like patients. No de novo variants emerged in REV3L and PLXND1. We then proceeded with a cohort analysis to identify possible common causative genes among all patients and a trio-based analysis using an in silico panel of candidate genes. However, identified variants emerging from both approaches were considered unlikely to be causative of MBS, mainly due to the lack of clinical overlap. In conclusion, despite this large cohort, WES failed to identify mutations possibly associated with MBS, further supporting the heterogeneity of this syndrome, and suggesting the need for integrated omics approaches to identify the molecular causes underlying MBS development.
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页数:13
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