Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Dumitrescu AM, Liao XH, Best TB et al (2004) A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 74(1):168–175
Arjona FJ, de Vrieze E, Visser TJ et al (2011) Identification and functional characterization of zebrafish solute carrier Slc16a2 (Mct8) as a thyroid hormone membrane transporter. Endocrinology 152(12):5065–5073
Schwartz CE, Stevenson RE (2007) The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Pract Res Clin Endocrinol Metab 21(2):307–321
Krude H, Biebermann H, Schuelke M et al (2020) Allan-Herndon-Dudley-syndrome: considerations about the brain phenotype with implications for treatment strategies. Exp Clin Endocrinol Diabetes 128(6–07):414–422
Gika AD, Siddiqui A, Hulse AJ et al (2010) White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene. Dev Med Child Neurol 52(5):475–482
Masnada S, Groenweg S, Saletti V et al (2019) Novel mutations in SLC16A2 associated with a less severe phenotype of MCT8 deficiency. Metab Brain Dis 34(6):1565–1575
Visser WE, Jansen J, Friesema EC et al (2009) Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations. Hum Mutat 30(1):29–38
Frints SG, Lenzner S, Bauters M et al (2008) MCT8 mutation analysis and identification of mthe first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. Eur J Hum Genet 16(9):1029–1037
Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L). Nature 190:372–3
Russell LB (1963) Mammalian X-chromosome action: inactivation limited in spread and region of origin. Science 140(3570):976–978
Brown CJ, Ballabio A, Rupert JL et al (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349(6304):38–44
Brockdorff N, Ashworth A, Kay GF et al (1991) Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature 351(6324):329–331
Jeon Y, Lee JT (2011) YY1 tethers Xist RNA to the inactive X nucleation center. Cell 146(1):119–133
Tian D, Sun S, Lee JT (2010) The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell 143:390–403
Yan F, Wang X, Zeng Y (2019) 3D genomic regulation of lncRNA and Xist in X chromosome. Semin Cell Dev Biol 90:174–180
Chao W, Huynh KD, Spencer RJ et al (2002) CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295(5553):345–347
Sun S, Del Rosario BC, Szanto A et al (2013) Jpx RNA activates Xist by evicting CTCF. Cell 153(7):1537–1551
Chureau C, Chantalat S, Romito A et al (2010) Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Hum Mol Genet 20(4):705–718
Hosoi Y, Soma M, Shiura H et al (2018) Publisher Correction: Female mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype. Nat Commun 9(1):4618 (Erratum)
Furlan G, Gutierrez Hernandez N, Huret C et al (2018) The Ftx noncoding locus controls X chromosome inactivation independently of its RNA products. Mol Cell 70(3):462-472.e8
Jonkers I, Barakat TS, Achame EM et al (2009) RNF12 is an X-encoded dose-dependent activator of X chromosome inactivation. Cell 139(5):999–1011
Gontan C, Achame EM, Demmers J et al (2012) RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature 485(7398):386–390
Sado T, Hoki Y, Sasaki H (2005) Tsix silences Xist through modification of chromatin structure. Dev Cell 9:159–165
Barakat TS, Loos F, van Staveren S et al (2014) The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing. Mol Cell 53(6):965–978
Ethics approval/consent to participate
Written informed consent was obtained in accordance with institutional requirements and the study fulfilled the principles of the Declaration of Helsinki.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Quesada-Espinosa, J.F., Garzón-Lorenzo, L., Lezana-Rosales, J.M. et al. First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center. Neurogenetics 22, 343–346 (2021). https://doi.org/10.1007/s10048-021-00660-7
- Allan-Herndon-Dudley syndrome
- X chromosome inactivation