Diagnosis of mosaic mutations in the MEN1 gene by next generation sequencing

in European Journal of Endocrinology
Correspondence should be addressed to A Tabarin; Email: antoine.tabarin@chu-bordeaux.fr

(A Tabarin and M-F Odou contributed equally to the study)

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We recently read with interest the review article of Persani et al. (1) who highlighted the occurrence of unexpected results obtained by next generation sequencing (NGS) with the identification of novel candidate genes or variants in non-coding regions. In complement to their review, we report herein for the first time two cases of MEN1 mosaic mutations identified only by NGS, a finding that emphasizes the usefulness of this tool in current endocrine practice.

Case 1

The proband was a 68-year-old man diagnosed at the age of 45 years with primary hyperparathyroidism (PHPT) in the

 

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    Genetic analysis in case n°2. (A) MEN1 Sanger sequencing of the proband: c.794G>A p.(Trp265*) heterozygous. (B) MEN1 Sanger sequencing of the father: no sequence variation detected. (C) MEN1 NGS sequencing of the father: mosaicism at the level of 6% of mutated alleles for c.794G>A p.(Trp265*). (D) Detail of the reads obtained by NGS.

References

1

PersaniLde FilippisTColomboCGentiliniD. Genetic diagnosis of endocrine diseases by NGS: novel scenarios and unpredictable results and risks. European Journal of Endocrinology 2018 179 R111R123. (https://doi.org/10.1530/EJE-18-0379)

2

IzawaKHijikataATanakaNKawaiTSaitoMKGoldbach-ManskyRAksentijevichIYasumiTNakahataTHeikeT et al. Detection of base substitution-type somatic mosaicism of the NLRP3 gene with >99.9% statistical confidence by massively parallel sequencing. DNA Research 2012 19 142152. (https://doi.org/10.1093/dnares/dsr047)

3

SpierIDrichelDKerickMKirfelJHorpaopanSLanerAHolzapfelSPetersSAdamRZhaoB et al. Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases. Journal of Medical Genetics 2016 53 172179. (https://doi.org/10.1136/jmedgenet-2015-103468)

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5

BuffetASmatiSMansuyLMenaraMLebrasMHeymannMFSimianCFavierJMuratACariouB et al. Mosaicism in HIF2A- related polycythemia-paraganglioma syndrome. Journal of Clinical Endocrinology and Metabolism 2014 99 E369E373. (https://doi.org/10.1210/jc.2013-2600)

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FarookSKannappanDKenzSLallooFTrainerPBrabantG. MEN-1 mosaic: the founder of a family. Endocrine Abstracts 2011 25 P196.

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MolatoreSPellegataNS. The MENX syndrome and p27: relationships with multiple endocrine neoplasia. Progress in Brain Research 2010 182 295320. (https://doi.org/10.1016/S0079-6123(10)82013-8)

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