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Left-sided congenital heart lesions in mosaic Turner syndrome

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Abstract

In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-β-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.

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Abbreviations

AAAD:

Acute type A aortic dissection

ACTA2:

Actin, alpha-2, smooth muscle, aorta [MIM:102620] cytogenetic location:10q23.31

AGTR1:

Angiotensin II receptor type 1 [MIM:106165] cytogenetic location:3q24

AGTR2:

Angiotensin II receptor type 2 [MIM:300034] cytogenetic location:Xq23

AngII:

Angiotensin II

AS:

Aortic stenosis

AZF:

Azoospermia factor

BAV:

Bicuspid aortic valve

bp:

Base pair

CEP:

DNA probe specific for the alpha satellite (centromeric) region

cGMP:

Cyclic guanosine monophosphate

CHD:

Congenital heart disease

CNV:

Copy number variant

COA:

Aortic coarctation

der(Y):

Derivative of Y chromosome

DNA:

Deoxyribonucleic acid

EDTA:

Ethylenediaminetetraacetic acid

FISH:

Fluorescence in situ hybridization

idic:

Isodicentric

KCl:

Potassium chloride

LSI:

Locus-specific identifier probe

MAT2A:

Methionine adenosyltransferase II, alpha [MIM:601468] cytogenetic location:2p11.2

MFAP5:

Microfibrillar-associated protein 5 [MIM:601103] cytogenetic location:12p13.31

MRI:

Magnetic resonance imaging

MYH11:

Myosin, heavy chain 11, smooth muscle [MIM:160745] cytogenetic location:16p13.11

MYLK:

Myosin light chain kinase [MIM:600922] cytogenetic location:3q21.1

NANOGP1:

NANOG homeobox pseudogene 1 (NCBI Gene ID:404635) cytogenetic location:12p13.31

PCR:

Polymerase chain reaction

PRKG1:

Protein kinase, cGMP-dependent regulatory, type I [MIM:176894] cytogenetic location:10q11.2-q21.1

RHG banding:

Reverse banding using heat and giemsa

SHOX:

Short stature homeobox gene [MIM:312865] cytogenetic location:Xp22.33

SLC2A14:

Solute carrier family 2 (facilitated glucose transporter), member 14 pseudogene [MIM:611039] cytogenetic location:12p13.31

SLC2A3:

Solute carrier family 2 (facilitated glucose transporter), member 3 pseudogene [MIM:138170] cytogenetic location:12p13.31

SMAD 3:

Mothers against decapentaplegic, DroSophila, homolog 3 [MIM:603109] cytogenetic location:15q22.33

SMAD:

Contraction of Sma and Mad, homologs of both the Drosophila protein, mothers against decapentaplegic (MAD) and the Caenorhabditis elegans protein SMA from gene sma for small body size

SRY:

Sex-determining Region Y [MIM:480000] cytogenetic location:Yp11.2

STS:

Sequence-tagged site

TGFBR1:

Transforming growth factor-beta receptor, type I [MIM:190181] cytogenetic location:9q22.33

TGFBR2:

Transforming growth factor-beta receptor, type II [MIM:190182] cytogenetic location:3p24.1

TGF-β:

Transforming growth factor-beta

vs:

Versus

TS:

Turner syndrome

ZFX/Y:

Sequences homologous to the human X- and Y-borne zinc finger protein genes

ZFX:

Zinc finger protein, X-linked [MIM:314980] cytogenetic location:Xp22.11

ZFY:

Zinc finger protein, Y-linked [MIM:490000] cytogenetic location:Yp11.2

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Acknowledgements

We thank the parents of the girl described for allowing us to share her details.

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Authors and Affiliations

  1. Department of Histology: UR17ES36 Genomics of signalopathies in the Service of Medicine, Medical University of Sfax, Av. Majida Boulila, 3029, Sfax, Tunisia

    Nouha Bouayed Abdelmoula, Balkiss Abdelmoula, Walid Smaoui, Rim Louati, Samir Aloulou, Wafa Aloulou, Fatma Abid, Senda Kammoun, Khaled Trigui, Olfa Bedoui, Hichem Denguir, Souad Mallek, Mustapha Ben Aziza, Jamila Dammak, Oldez Kaabi, Nawel Abdellaoui, Fatma Turki, Asma Kaabi, Wafa Kamoun, Jihen Jabeur, Wided Ltaif, Kays Chaker, Haytham Fourati, Samir M’rabet, Hedi Ben Ameur, Naourez Gouia & Mohamed Nabil Mhiri

  2. Department of Histology, Medical University of Sfax, Sfax, Tunisia

    Nouha Bouayed Abdelmoula & Tarek Rebai

  3. Department of Cardiology, Hedi Chaker Hospital of Sfax, Sfax, Tunisia

    Imen Trabelsi

  4. Department of Urology, Habib Bourguiba Hospital of Sfax, Sfax, Tunisia

    Walid Smaoui & Mohamed Nabil Mhiri

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  1. Nouha Bouayed Abdelmoula
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  2. Balkiss Abdelmoula
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  18. Fatma Turki
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Corresponding author

Correspondence to Nouha Bouayed Abdelmoula.

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the reported case.

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Communicated by S. Hohmann.

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Bouayed Abdelmoula, N., Abdelmoula, B., Smaoui, W. et al. Left-sided congenital heart lesions in mosaic Turner syndrome. Mol Genet Genomics 293, 495–501 (2018). https://doi.org/10.1007/s00438-017-1398-x

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  • DOI: https://doi.org/10.1007/s00438-017-1398-x

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