Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene
Abstract Background Wolf–Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4. To establish a genotype–phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients....
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doaj-329170b053014f82af7fa4f13e5faf632021-03-11T12:07:18ZengBMCMolecular Cytogenetics1755-81662021-02-011411910.1186/s13039-021-00531-8Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate geneKhouloud Rjiba0Hédia Ayech1Olfa Kraiem2Wafa Slimani3Afef Jelloul4Imen Ben Hadj Hmida5Nabiha Mahdhaoui6Ali Saad7Soumaya Mougou-Zerelli8Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalPediatric Department, Farhat Hached University Teaching HospitalPediatric Department, Regional HospitalLaboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalLaboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalLaboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalPediatric Department, Farhat Hached University Teaching HospitalLaboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalLaboratory of Human Cytogenetics, Molecular Genetics and Biology of Reproduction, Farhat Hached University Teaching HospitalAbstract Background Wolf–Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4. To establish a genotype–phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1 was a boy of 1-year-old, presented a typical WHS phenotype while patient 2, is a boy of 2 days presented an hypospadias, a micropenis and a cryptorchidie in addition to the typical WHS phenotype. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used. Results Results of the analysis showed that patient 2 had a greater deletion size (4.8 Mb) of chromosome 4 than patient 1 (3.4 Mb). Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. If we analyze the uncommon deleted region between patient1 and patient 2 we found that the Muscle Segment Homeobox (MSX1) gene is included in this region. MSX1 is a critical transcriptional repressor factor, expressed in the ventral side of the developing anterior pituitary and implicated in gonadotrope differentiation. Msx1 acts as a negative regulatory pituitary development by repressing the gonadotropin releasing hormone (GnRH) genes during embryogenesis. We hypothesized that the deletion of MSX1 in our patient may deregulate the androgen synthesis. Conclusion Based on the MSX1 gene function, its absence might be indirectly responsible for the hypospadias phenotype by contributing to the spatiotemporal regulation of GnRH transcription during development.https://doi.org/10.1186/s13039-021-00531-8HypospadiasArray CGHFISHWolf–Hirschhorn syndromeMSX1gene |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Khouloud Rjiba Hédia Ayech Olfa Kraiem Wafa Slimani Afef Jelloul Imen Ben Hadj Hmida Nabiha Mahdhaoui Ali Saad Soumaya Mougou-Zerelli |
spellingShingle |
Khouloud Rjiba Hédia Ayech Olfa Kraiem Wafa Slimani Afef Jelloul Imen Ben Hadj Hmida Nabiha Mahdhaoui Ali Saad Soumaya Mougou-Zerelli Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene Molecular Cytogenetics Hypospadias Array CGH FISH Wolf–Hirschhorn syndrome MSX1gene |
author_facet |
Khouloud Rjiba Hédia Ayech Olfa Kraiem Wafa Slimani Afef Jelloul Imen Ben Hadj Hmida Nabiha Mahdhaoui Ali Saad Soumaya Mougou-Zerelli |
author_sort |
Khouloud Rjiba |
title |
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene |
title_short |
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene |
title_full |
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene |
title_fullStr |
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene |
title_full_unstemmed |
Disorders of sex development in Wolf–Hirschhorn syndrome: a genotype–phenotype correlation and MSX1 as candidate gene |
title_sort |
disorders of sex development in wolf–hirschhorn syndrome: a genotype–phenotype correlation and msx1 as candidate gene |
publisher |
BMC |
series |
Molecular Cytogenetics |
issn |
1755-8166 |
publishDate |
2021-02-01 |
description |
Abstract Background Wolf–Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4. To establish a genotype–phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1 was a boy of 1-year-old, presented a typical WHS phenotype while patient 2, is a boy of 2 days presented an hypospadias, a micropenis and a cryptorchidie in addition to the typical WHS phenotype. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used. Results Results of the analysis showed that patient 2 had a greater deletion size (4.8 Mb) of chromosome 4 than patient 1 (3.4 Mb). Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. If we analyze the uncommon deleted region between patient1 and patient 2 we found that the Muscle Segment Homeobox (MSX1) gene is included in this region. MSX1 is a critical transcriptional repressor factor, expressed in the ventral side of the developing anterior pituitary and implicated in gonadotrope differentiation. Msx1 acts as a negative regulatory pituitary development by repressing the gonadotropin releasing hormone (GnRH) genes during embryogenesis. We hypothesized that the deletion of MSX1 in our patient may deregulate the androgen synthesis. Conclusion Based on the MSX1 gene function, its absence might be indirectly responsible for the hypospadias phenotype by contributing to the spatiotemporal regulation of GnRH transcription during development. |
topic |
Hypospadias Array CGH FISH Wolf–Hirschhorn syndrome MSX1gene |
url |
https://doi.org/10.1186/s13039-021-00531-8 |
work_keys_str_mv |
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