To the point about etiopathogenetic causes of Marfan-like phenotype (marfanoid appearance) formation


DOI: https://dx.doi.org/10.18565/therapy.2020.6.88-92

Smolnova T.Yu., Trofimov D.Yu., Chuprynin V.D., Nechaeva G.I.

1) National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Acad. V.I. Kulakov of the Ministry of Healthcare of Russia, Moscow; 2) Omsk State Medical University of the Ministry of Healthcare of Russia
Connective tissue dysplasia syndrome (CTD) is characterized by multiorganicity, polysystemicity, the presence of erased and crossed forms, the absence of criteria for molecular diagnostics due to its heterogeneity. Therefore, the search for new diagnostical methods to confirm the form of CTD is extremely actual. For example, such monogenic syndromes as Lois–Dietz syndrome, Shprinzen–Goldberg syndrome and Marfan syndrome, although caused by various genetic defects, are at the same time characterized by a common clinical picture and have common chains in microfibril assembly disorders. The aim of the study was to diagnose CTD forms using a unified panel for genetic polymorphisms and genetic mutations’ identification.
Material and methods. Four female patients with a Marfan-like phenotype (marfanoid appearance) who were admitted to a gynecological clinic for surgical treatment were examined. Specially developed unified panel for detecting CTD genetic mutations, created on the basis of high throughput sequencing (NGS) was used in the study.
Results. The mechanisms of the formation of Marfan’s syndrome and clinical picture-related syndromes, as well as the Marfan-like phenotype (Marfanoid appearance), depending on the type of genetic mutation and the expression level of transforming growth factor β (TGF-β) in the extracellular matrix, are considered. The role of the mutation in the ADAMTSL4 gene in the Marfan-like phenotype (Marfanoid appearance), Marfan syndrome, the presence of syndromic or isolated Ectopia lentis et pupillae (225200) and Ectopia lentis, isolated, autosomal recessive (225100) was shown. The role of the mutation in the ADAMTSL4 gene and the ADAMTS family of proteins as highly informative criteria for the diagnosis of CTD has been also established.
Conclusion. A unified panel for detecting genetic polymorphisms and genetic mutations in female patients of different age groups in obstetrics and gynecology allows to perform CTD diagnosing. Mutation in the ADAMTSL4 gene can occur in patients with a marfan-like phenotype (marfanoid appearance) without the Ectopia lentis development. It may be based on a decrease in the expression of ADAMTSL4 protein, which disrupts FBN1 (fibrillin) deposition in microfibrils.
Keywords: fibrillin, ADAMTSL4 gene mutation, Marfan-like phenotype, Ectopia lentis, transforming growth factor β, marfanoid appearance, connective tissue dysplasia
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About the Autors

Tatiana Yu. Smolnova, MD, senior associate of the surgery Department of the National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Acad. V.I. Kulakov of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 4 Akademika Oparina Str. Tel.: +7 (926) 310-80-90. E-mail: smoltat@list.ru. ORCID: 0000-0003-3543-651X
Dmitry Yu. Trofimov, MD, professor of RAS, Director of the Institute of Reproductive Genetics of the National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Acad. V.I. Kulakov of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 4 Akademika Oparina Str. Tel.: +7 (495) 438-78-33. E-mail: d_Trofimov @oparina4.ru
Vladimir D. Chuprynin, PhD, head of surgery Department of the National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Acad. V.I. Kulakov of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 4 Akademika Oparina Str. Tel.: +7 (495) 438-78-33. E-mail: v_chuprynin@oparina4.ru
Galina I. Nechaeva, MD, professor, head of the Department of internal diseases and family medicine of Omsk State Medical University of the Ministry of Healthcare of Russia. Address: 644043, Omsk, 12 Lenina Str. Tel.: +7 (3812) 23-67-00. E-mail: profnechaeva@yandex.ru. ORCID: 0000-0002-2255-128X


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