<i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH)
TITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that <i>Titf1</i> null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this stud...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Children |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9067/9/8/1108 |
| _version_ | 1797410829154385920 |
|---|---|
| author | Maria Eugenia Gulino Giuseppe Martucciello Elio Biffali Patrizia Morbini Roberta Patti Marco Borra Maria Grazia Scuderi |
| author_facet | Maria Eugenia Gulino Giuseppe Martucciello Elio Biffali Patrizia Morbini Roberta Patti Marco Borra Maria Grazia Scuderi |
| author_sort | Maria Eugenia Gulino |
| collection | DOAJ |
| description | TITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that <i>Titf1</i> null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this study, we aim to evaluate the role of <i>TITF1</i> in the pathogenesis of congenital diaphragmatic hernia (CDH) in humans. We investigated <i>TITF1</i> expression in human trachea and lungs and performed direct mutation analysis in a CDH population. We studied 13 human fetuses at 14 to 24 weeks of gestation. Five μm sections were fixed in paraformaldehyde and incubated with anti-TITF1 primary antibody. Positive staining was visualized by biotinylated secondary antibody. We also performed <i>TITF1</i> screening on genomic DNA extracted from peripheral blood of 16 patients affected by CDH and different degrees of PH, searching for mutations, insertions, and/or deletions, by sequencing the exonic regions of the gene. Histochemical studies showed positive brown staining of fetal follicular thyroid epithelium, normal fetal trachea, and normal fetal lung bronchial epithelium. Fetal esophageal wall was immunohistochemically negative. Molecular genetic analysis showed complete identity between the sequences obtained and the Wild Type (WT) form of the gene in all cases. No mutation, insertion and/or deletion was detected. Although <i>TITF1</i> is expressed in the human fetal lung and has been considered to have a role in the pathogenesis of PH in CDH, the results of our study do not support the hypothesis that <i>TITF1</i> mutations play a key role in the etiopathogenesis of CDH. |
| first_indexed | 2024-03-09T04:35:55Z |
| format | Article |
| id | doaj.art-73f25602b0234c2794e5d9b97743a2be |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-09T04:35:55Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-73f25602b0234c2794e5d9b97743a2be2023-12-03T13:28:00ZengMDPI AGChildren2227-90672022-07-0198110810.3390/children9081108<i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH)Maria Eugenia Gulino0Giuseppe Martucciello1Elio Biffali2Patrizia Morbini3Roberta Patti4Marco Borra5Maria Grazia Scuderi6UOC di Chirurgia Pediatrica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyPediatric Surgery DiNOGMI, University of Genova, 16147 Genoa, ItalyStazione Zoologica “A. Dohrn”, 80121 Naples, ItalyUOC Anatomia Patologica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, ItalyUOC di Chirurgia Pediatrica, Ospedale Policlinico San Marco, 95121 Catania, ItalyStazione Zoologica “A. Dohrn”, 80121 Naples, ItalyUOC di Chirurgia Pediatrica, Ospedale Policlinico San Marco, 95121 Catania, ItalyTITF1 (Thyroid Transcription Factor-1) is a homeodomain-containing transcription factor. Previous studies showed that <i>Titf1</i> null mice are characterized by failure of tracheo-oesophageal separation and impaired lung morphogenesis resulting in Pulmonary Hypoplasia (PH). In this study, we aim to evaluate the role of <i>TITF1</i> in the pathogenesis of congenital diaphragmatic hernia (CDH) in humans. We investigated <i>TITF1</i> expression in human trachea and lungs and performed direct mutation analysis in a CDH population. We studied 13 human fetuses at 14 to 24 weeks of gestation. Five μm sections were fixed in paraformaldehyde and incubated with anti-TITF1 primary antibody. Positive staining was visualized by biotinylated secondary antibody. We also performed <i>TITF1</i> screening on genomic DNA extracted from peripheral blood of 16 patients affected by CDH and different degrees of PH, searching for mutations, insertions, and/or deletions, by sequencing the exonic regions of the gene. Histochemical studies showed positive brown staining of fetal follicular thyroid epithelium, normal fetal trachea, and normal fetal lung bronchial epithelium. Fetal esophageal wall was immunohistochemically negative. Molecular genetic analysis showed complete identity between the sequences obtained and the Wild Type (WT) form of the gene in all cases. No mutation, insertion and/or deletion was detected. Although <i>TITF1</i> is expressed in the human fetal lung and has been considered to have a role in the pathogenesis of PH in CDH, the results of our study do not support the hypothesis that <i>TITF1</i> mutations play a key role in the etiopathogenesis of CDH.https://www.mdpi.com/2227-9067/9/8/1108congenital diaphragmatic hernia (CDH)pulmonary hypoplasia (PH)molecular geneticshistochemistry<i>TITF1</i> |
| spellingShingle | Maria Eugenia Gulino Giuseppe Martucciello Elio Biffali Patrizia Morbini Roberta Patti Marco Borra Maria Grazia Scuderi <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) Children congenital diaphragmatic hernia (CDH) pulmonary hypoplasia (PH) molecular genetics histochemistry <i>TITF1</i> |
| title | <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) |
| title_full | <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) |
| title_fullStr | <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) |
| title_full_unstemmed | <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) |
| title_short | <i>TITF1</i> Screening in Human Congenital Diaphragmatic Hernia (CDH) |
| title_sort | i titf1 i screening in human congenital diaphragmatic hernia cdh |
| topic | congenital diaphragmatic hernia (CDH) pulmonary hypoplasia (PH) molecular genetics histochemistry <i>TITF1</i> |
| url | https://www.mdpi.com/2227-9067/9/8/1108 |
| work_keys_str_mv | AT mariaeugeniagulino ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT giuseppemartucciello ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT eliobiffali ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT patriziamorbini ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT robertapatti ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT marcoborra ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh AT mariagraziascuderi ititf1iscreeninginhumancongenitaldiaphragmaticherniacdh |