Genetics in Medicine (2022) 24, 2206
www.journals.elsevier.com/genetics-in-medicine
LETTER TO THE EDITOR
Response to Kossmann Ferraz et al
To the Editor:
1
In their letter, Kossmann Ferraz et al reported a patient
affected by a neurodevelopmental disorder and carrying a
germline de novo loss-of-function variant (c.971del;p.
(pro324Glnfs*18)) in MED12L. This boy also carries 2
de novo chromosomal balanced reciprocal translocations:
46,XY,t(1;2)(p33;p22),t(5;9)(p15;q21). This lead them to
ask if a loss-of-function MED12L variant could induce
chromosomal instability and be responsible for a de novo
rearrangement.
In our study, we had reported 7 patients carrying a
de novo loss-of-function variant in MED12L.2 In total, 4
patients had normal karyotype. One of the patient (indi-
vidual 5) was also carrying a balanced translocation: 46,XY,
t(9p13;18q12.2). Parental karyotypes were not available but
we could notice that the couple experienced 4 miscarriages
that could suggest an inherited translocation.
Although the co-occurrence of 3 de novo events in the
patient reported by Kossmann Ferraz et al1 is intriguing, it
might be premature to conclude that a direct causality link
between a germline MED12L variant and the occurrence of
chromosomal rearrangements.
To date, MED12L is mostly involved in transcription. To
the best of our knowledge, de novo chromosomal rear-
rangements are not reported with a higher frequency in
patients with other mediatorpathy.
Still, considering that we are, at this time, not able to
determine whether this case occurred by chance, it might be
interesting to perform a karyotype for any individual who
would be diagnosed with this syndrome.
Conflict of Interest
The authors declare no conflicts of interest.
Mathilde Nizon*
Bertrand Isidor
Service de Génétique Médicale and L’institut du Thorax, CHU Nantes,
Nantes Université, CNRS, INSERM, Nantes, France
*Correspondence and requests for materials should be addressed to
Mathilde Nizon, Service de Génétique Médicale, CHU Nantes,
Nantes Université, CNRS, INSERM, l’institut du thorax, F-44000
Nantes, France.
E-mail address: mathilde.nizon@chu-nantes.fr
Received 27 June 2022; Accepted 30 June 2022
Available online 3 August 2022
© 2022 American College of Medical Genetics and Genomics.
Published by Elsevier Inc. All rights reserved.
http://doi.org/10.1016/j.gim.2022.06.012
References
1. Kossmann Ferraz M, Esposito AC, Schmidt C, Lima FD, MA Vargas R.
Correspondence on “Variants in MED12L, encoding a subunit of the
mediator kinase module, are responsible for intellectual disability associated
with transcriptional defect” by Nizon et al. Genet Med. 2022;24:2204–2205.
2. Nizon M, Laugel V, Flanigan KM, et al. Variants in MED12L, encoding
a subunit of the mediator kinase module, are responsible for intellectual
disability associated with transcriptional defect. Genet Med.
2019;21(12):2713-2722. Published correction appears in Genet Med.
2019;21(11):2663. https://doi.org/10.1038/s41436-019-0557-3.