Semih Bolu, Abdulvahit Aşık, Özden Öztürk

PROP-1 geninde homozigot delesyon mutasyonuna sahip iki kız kardeş

PROP-1 genindeki bozukluklar somatrop, tirotrop, laktotrop, gonadotrop ve kortikotropları etkileyerek klinik bulgulara yol açar. PROP-1 gen mutasyonu olan vakalarda ilk bulgu büyüme hormonu eksikliği ve santral hipotiroidi ile ilişkili büyüme geriliğidir. Diğer hormon eksiklikleri zamanla eklenir. Burada, PROP-1 geninde silme mutasyonu olan iki kız kardeşi bildirdik. Ebeveynler birinci derece kuzendi. Büyüme gelişme geriliği ve boy kısalığı yakınması ile başvuran olgulardan indeks kız hasta 4,6 yaşında, kız kardeşi ise 1,9 yaşındaydı. Her iki kız kardeşte de santral hipotiroidizm ve büyüme hormonu eksikliği (BH) belirlendi. Genetik analizde, PROP-1 geninde homozigot delesyon mutasyonu saptandı. Büyüme hormon eksikliği ve santral hipotiroidi ile başvuran hastalarda PROP-1 mutasyonu düşünülmeli ve genetik analiz ile tanı doğrulanmalıdır.

Two sisters with homozygous deletion mutation in the PROP-1 gene

Defects in the PROP-1 gene produce clinical findings by affecting somatotrophs, thyrotrophs,lactotrophs, gonadotrophs and corticotrophs. The first finding in cases with PROP-1 gene mutation isgrowth retardation associated with growth hormone (GH) deficiency and central hypothyroidism. Otherhormone deficiencies are added over time. We describe two sisters with deletion mutation in thePROP-1 gene. The parents were first-degree cousins. The female patient identified as the index casewas 4.6 and the other sister was 1.9 years old when they presented with failure to thrive and shortstature. Central hypothyroidism and GH deficiency was determined in both sisters. Homozygousdeletion mutation was determined in the PROP-1 gene at genetic analysis. PROP-1 mutation shouldbe considered in patients presenting with combined GH deficiency and central hypothyroidism, and thediagnosis must be confirmed with genetic analysis.

PDF

___

1. Böttner A, Keller E, Kratzsch J, et al. PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis. J Clin Endocrinol Metab 2004; 89 (10): 5256-65.
2. Vieira TC, Boldarine VT, Abucham J. Molecul aranalysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arq Bras Endocrinol Metabol 2007; 51 (7): 1097-103.
3. Bertko E, Klammt J, Dusatkova P, et al. Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes. J Hum Genet 2017; 62 (8): 755-62.
4. Penta L, Bizzarri C, Panichi M, et al. Identification of a Novel PROP1 Mutation in a Patient with Combined Pituitary Hormone Deficiency and Enlarged Pituitary. Int J Mol Sci 2019; 20 (8): 1875.
5. Lebl J, Vosáhlo J, Pfaeffle RW, et al. Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects. Eur J Endocrinol 2005; 153 (3): 389-96.
6. Lau E, Freitas P, Coutinho E, Lemos MC, Carvalho D. Familial combined pituitary hormone deficiency by a mutation in PROP1: 4 of 7 brothers affected. Revista Portuguesa de Endocrinologia, Diabetes e Metabolismo 2016; 11 (1): 41–4.
7. Deladoëy J, Flück C, Büyükgebiz A, et al. Hot spot in the PROP1 gene responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 1999; 84 (5): 1645-50.
8. Bulut FD, Özdemir Dilek S, Kotan D, Mengen E, Gürbüz F, Yüksel B. Mutations With in the Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency. J ClinRes Pediatr Endocrinol 2020; 12 (3): 261-8.
9. Gorar S, Turkkahraman D, Yararbas K. A Large PROP1 Gene Deletion in a Turkish Pedigree. Case Rep Endocrinol 2018; 2018: 2403430.
10.Abrão MG, Leite MV, Carvalho LR, et al. Combined pituitary hormone deficiency (CPHD) dueto a complete PROP1 deletion. Clin. Endocrinol (Oxf) 2006; 65 (3): 294-300.