Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency
<i>Background and Objectives</i>: Combined pituitary hormone deficiency (CPHD) is a rare heterogeneous disease. It is characterized by the deficiency of growth hormone (GH) and shortage of at least one or more other hormones of the pituitary gland including thyroid-stimulating hormone (T...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/3/474 |
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| author | Ahmed M. Almatrafi Ali M. Hibshi Sulman Basit |
| author_facet | Ahmed M. Almatrafi Ali M. Hibshi Sulman Basit |
| author_sort | Ahmed M. Almatrafi |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Combined pituitary hormone deficiency (CPHD) is a rare heterogeneous disease. It is characterized by the deficiency of growth hormone (GH) and shortage of at least one or more other hormones of the pituitary gland including thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Rare pathogenic variants in nearly 30 genes have been identified as an underlying cause of CPHD pathogenicity. Among these genes, paired-like homeobox 1 (<i>PROP1</i>) has been reported to be the most common cause of CPHD. <i>Materials and Methods</i>: In the present study, we investigated a large family of Saudi origin with three adult sisters suffering from short stature in combination of secondary amenorrhea. <i>Results</i>: Whole-exome sequencing followed by Sanger sequencing shows a homozygous missense variant (NM_006261.5; c.211C > T; p.R71C) in the <i>PROP1</i> gene segregating with the disease phenotype within the family. In silico analysis studies show that this variant is highly conserved among several orthologues and is predicted as likely pathogenic using various bioinformatics tools. <i>Conclusions</i>: Our finding presents the first Saudi familial case of autosomal recessive form of CPHD caused by the <i>PROP1</i> variant. |
| first_indexed | 2024-03-11T06:12:05Z |
| format | Article |
| id | doaj.art-22af5374c8c64e05aef1ac4f230816df |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T06:12:05Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-22af5374c8c64e05aef1ac4f230816df2023-11-17T12:31:09ZengMDPI AGMedicina1010-660X1648-91442023-02-0159347410.3390/medicina59030474Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone DeficiencyAhmed M. Almatrafi0Ali M. Hibshi1Sulman Basit2Department of Biology, College of Science, Centre for Genetics and Inherited Diseases, Taibah University Al Madinah, Al Munawarah 42353, Saudi ArabiaDepartment of Obstetrics & Gynecology, King Sulman Medical City-Madinah Maternity and Children Hospital, Almadinah Almunawwarah 42319, Saudi ArabiaDepartment of Biochemistry, College of Medicine, Centre for Genetics and Inherited Diseases, Taibah University Al Madinah, Al Munawarah 42353, Saudi Arabia<i>Background and Objectives</i>: Combined pituitary hormone deficiency (CPHD) is a rare heterogeneous disease. It is characterized by the deficiency of growth hormone (GH) and shortage of at least one or more other hormones of the pituitary gland including thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Rare pathogenic variants in nearly 30 genes have been identified as an underlying cause of CPHD pathogenicity. Among these genes, paired-like homeobox 1 (<i>PROP1</i>) has been reported to be the most common cause of CPHD. <i>Materials and Methods</i>: In the present study, we investigated a large family of Saudi origin with three adult sisters suffering from short stature in combination of secondary amenorrhea. <i>Results</i>: Whole-exome sequencing followed by Sanger sequencing shows a homozygous missense variant (NM_006261.5; c.211C > T; p.R71C) in the <i>PROP1</i> gene segregating with the disease phenotype within the family. In silico analysis studies show that this variant is highly conserved among several orthologues and is predicted as likely pathogenic using various bioinformatics tools. <i>Conclusions</i>: Our finding presents the first Saudi familial case of autosomal recessive form of CPHD caused by the <i>PROP1</i> variant.https://www.mdpi.com/1648-9144/59/3/474combined pituitary hormone deficiency<i>PROP1</i>novel sequence variantwhole-exome sequencing |
| spellingShingle | Ahmed M. Almatrafi Ali M. Hibshi Sulman Basit Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency Medicina combined pituitary hormone deficiency <i>PROP1</i> novel sequence variant whole-exome sequencing |
| title | Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency |
| title_full | Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency |
| title_fullStr | Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency |
| title_full_unstemmed | Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency |
| title_short | Association of Homozygous <em>PROP1</em> Mutation in a Saudi Family with Combined Pituitary Hormone Deficiency |
| title_sort | association of homozygous em prop1 em mutation in a saudi family with combined pituitary hormone deficiency |
| topic | combined pituitary hormone deficiency <i>PROP1</i> novel sequence variant whole-exome sequencing |
| url | https://www.mdpi.com/1648-9144/59/3/474 |
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