International Clinical and Medical Case Reports Journal (ISSN: 2832-5788) | Volume 5, Issue 8 | Case Report | Open Access DOI
Amrit Kaur Kaler*
Amrit Kaur Kaler1*, Nisha Kaimal2 , Raghuram Sekhar3, Nishant Jindal4, Anaya Sharma1, Latika Arora1, Manali A1, Aditi Shirodkar1 1 Department of Molecular Pathology and Genomics, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
2 Department of Endocrinology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
3Diabetes & Bariatric Surgery, Vascular Surgery, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
4Department of Centre for Cancer (Clinical Haematology), Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
*Correspondence to: Amrit Kaur Kaler
Fulltext PDFA 40-year-old woman with a clinical diagnosis of combined pituitary hormone deficiency (CPHD-2) (OMIM# #262600), and recurrent thrombosis underwent whole-exome sequencing, which identified a likely pathogenic variant in the PROP1 (Prophet of Pit1) gene and Variant of Unknown Significance (VUS) in the PROC gene. The PROP1 gene encodes as a “later acting transcription factor” in pituitary development and encodes a paired-like homeodomain transcription factor that is necessary for expression of the POUF domain transcription factor 1. The Protein C (PROC) gene encodes protein C, a vitamin K-dependent anticoagulant that regulates blood coagulation by inactivating coagulation factors Va and VIIIa.
Mutations in the PROP1 gene can cause CPHD-2, which may manifest as short stature, hypothyroidism, growth retardation, delayed and incomplete secondary sexual development with infertility. This is due to deficiencies in thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and growth hormone (GH). Pathogenic variants in PROC cause protein C deficiency, an inherited thrombophilia that predisposes affected individuals to venous thromboembolism.
We report a case where a lady presented with short stature, C-spine fusion, short and stiff neck, multiple pituitary hormone deficiencies (LH, FSH, TSH, GH and Prolactin) and recurrent lower limb arterial thrombosis. She had primary amenorrhea, for which treatment was initiated at the age of 22 years. Genetic testing by exome sequencing enabled an accurate diagnosis of the underlying aetiology, with genotype – phenotype correlation which led to better disease management.
Amrit Kaur Kaler, Nisha Kaimal, Raghuram Sekhar, Nishant Jindal, Anaya Sharma, Latika Arora, Manali A, Aditi Shirodkar. A Novel Clinical Presentation of PROP1-Associated Combined Pituitary Hormone Deficiency with Severe Thrombosis: A Case Report. Int Clinc Med Case Rep Jour. 2026;5(8):1-6.