Genetic spectrum and predictors of mutations in four known genes in Asian Indian patients with growth hormone deficiency
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Genetic spectrum and predictors of mutations in four known genes in Asian Indian patients with growth hormone deficiency and orthotopic posterior pituitary: an emphasis on regional genetic diversity Shantanu Kale1 · Jugal V. Gada2 · Swati Jadhav1 · Anurag R. Lila1 · Vijaya Sarathi3 · Sweta Budyal1 · Hiren Patt1 · Manjunath R. Goroshi4 · Puja M. Thadani1 · Sneha Arya1 · Aparna A. Kamble1 · Virendra A. Patil1 · Shrikrishna Acharya5 · Shilpa Sankhe1 · Vyankatesh Shivane1 · Vijaya Raghavan1 · Tushar R. Bandgar1 · Nalini S. Shah1
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Context Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known. Aim Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort. Methods One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients. Results Of 102, 19.6% were familial cases. Height SDS, mean (SD) was − 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ ml (0–6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients. Conclusion At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD. Keywords Isolated growth hormone deficiency (IGHD) · Combined pituitary hormone deficiency (CPHD) · Short stature · GH1 · GHRHR · POU1FI · PROP1 · Regional diversity
Shantanu Kale and Jugal V. Gada are Joint Authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11102-020-01078-4) contains supplementary material, which is available to authorized users. * Virendra A. Patil [email protected] 1
Department of Endocrinology, Seth G.S. Medical College & KEM Hospital, Parel, Mumbai, Maharashtra 400012, India
Department of Endocrinology, Topiwala National Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India
2
Abbreviations GHD Growth hormone deficiency IGHD Isolated growth hormone deficiency
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