Lan ZhuOBGYN, email@example.com
Reply to Professor Kauffman’s editorial
MAYER-ROKITANSKY-KÜSTER-HAUSER SYNDROME (MÜLLERIAN AGENESIS): A WIDER WINDOW INTO ETHNIC PHENOTYPIC DIVERSITY. WHERE TO FROM HERE?
Comment on: Chen N, et al. Clinical feature of 1055 Chinese patients with Mayer-Rokitansky-Küster-Hauser syndrome: a nationwide multicentric study. Fertil Steril, accepted for publication.
Lan Zhu, M.D.,
from the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing 100730, China;
Conflicts of interest: none to declare
Dear Professor Kauffman,
Thank you very much for your insightful comment on our study. A detailed literature review including the physical and psychological effects of the disease on MRKH patients, the prevalence, the associated malformations, the complex and uncertain etiology, and the ethnic phenotypic diversities among different MRKH cohorts was conducted in your comment.
In clinical studies of MRKH, psychological counseling and peer support should be enhanced. A MRKH patient group was established based on the We-Chat platform in Peking Union Medical College Hospital since 2015. This We-Chat group currently has 493 members, of whom all but three obstetricians and one psychologist are MRKH patients diagnosed at our hospital. The oldest patient in the group is over 40 years old and the youngest patient is only 16 years old, and everyone in the group uses WeChat nicknames, thus protecting privacy. Troubles in gender relationships, life struggles, and fertility difficulties are often discussed in the group. Older patients are willing to offer their experience and courage when younger ones encounter the same problems they have encountered before. However, considering the high risk of MRKH patients show depressive and anxiety symptoms[1, 2], proper psychological assessment and psychotherapy in the psychology clinics should be further promoted.
We totally agree that given the multiple consequences of MRKH syndrome, in-depth etiological studies should be conducted in addition to clinical studies. In fact, the peripheral blood samples of MRKH sporadic patients and parents of some patients were also collected in addition to the collection of the clinical characteristics of these patients in the past 10 years in China. Till November 2017，exome sequencing was performed on 442 Chinese MRKH patients and 941 female control subjects. By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting variants in 7 genes: PAX8 (n =4), BMP4 (n=2), BMP7 (n=2), TBX6 (n=1), HOXA10 (n=1), EMX2 (n=1), and WNT9B (n=1), while LGD variants in these genes were not detected in control samples (p=1.27E-06). Further experiments to identify the mechanism of the top-three candidate-gene mutations (PAX8, BMP4 and BMP7) found above as cause of MRKH were performed now. To date, whole genome sequencing was performed on another 303 sporadic Chinese MRKH patients (including 105 trios). Analysis of the sequencing data is still in progress.
Thank you again for your comments and we look forward to working with more physicians interested in MRKH syndrome to explore the etiology of the disease and improve the quality of life in MRKH patients.
- Song S, Chen N, Duan YP, Kang J, Deng S, Pan HX et al. Anxiety symptoms in patients with Mayer-Rokitansky-Küster-Hauser syndrome: a cross-sectional study. Chin Med J (Engl) 2020;133:388-94.
- Chen N, Song S, Duan Y, Kang J, Deng S, Pan H et al. Study on depressive symptoms in patients with Mayer-Rokitansky-Küster-Hauser syndrome: an analysis of 141 cases. Orphanet journal of rare diseases 2020;15:121.
- Chen N, Zhao S, Jolly A, Wang L, Pan H, Yuan J et al. Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome. The American Journal of Human Genetics 2021.