Growth Hormone Receptor <i>(GHR)</i> 6Ω Pseudoexon Activation: A Novel Cause of Severe Growth Hormone Insensitivity
نویسندگان
چکیده
Abstract Context Severe forms of growth hormone insensitivity (GHI) are characterized by extreme short stature, dysmorphism, and metabolic anomalies. Objective This work aims to identify the genetic cause failure in 3 “classical” GHI individuals. Methods A novel intronic receptor gene (GHR) variant was identified, vitro splicing assays confirmed aberrant splicing. 6Ω pseudoexon GHR vector patient fibroblast analysis assessed consequences inclusion impact on function. Results We identified a homozygous (g.5:42700940T &gt; G, c.618+836T G), 44 bp downstream previously recognized 6Ψ mutation index patient. Two siblings also harbored compound heterozygosity with known c.181C T (R43X) mutation. In 151-bp mutant not wild-type constructs. Inclusion causes frameshift resulting nonfunctional truncated lacking transmembrane intracellular domains. The protein demonstrated extracellular accumulation diminished activation STAT5B signaling following GH stimulation. Conclusion Novel results loss function consistent severe phenotype. represents mechanism Laron syndrome is first deep causing postnatal failure. 2 kindreds originate from same town Campania, Southern Italy, implying common ancestry. Our findings highlight importance studying variation regions as monogenic disorders.
منابع مشابه
تأثیر پلی مورفیسم های ژن های هورمون رشد growth hormone و گیرنده ژن هورمون رشد growth hormone receptor روی برخی صفات اقتصادی بز مرغز ایران
در این پژوهش به بررسی وجود پلی مورفیسم در ناحیه پروموتور و اگزون 10 ژن های gh و ghr و ارتباط آنها با صفات رشد در بزهای مرغز پرداخته شد. بدین منظور از سیاهرگ وداج تعداد 160 بز مرغز موجود در ایستگاه اصلاح نژاد استان کردستان خونگیری و dna نمونه ها با استفاده از کیت استخراج گردید. قطعه 391 جفت بازی از ژن gh و 361 جفت بازی از ژن ghr تکثیر شدند. از تفاوت چندشکلی فضایی تک رشته ها (sscp) و توالی یابی ب...
Growth hormone insensitivity.
Growth hormone insensitivity (GHI) may be primary, caused by defects in the GH receptor, or further along the GH-insulin-like growth factor-I (IGF-I) axis, or secondary, resulting from a variety of illnesses or malnutrition affecting various steps in the pathway from the GH binding to IGF-I action. GH receptor deficiency, although rare, with only 229 cases reported, is the most common cause of ...
متن کاملNovel Growth Hormone-Releasing Hormone Receptor Gene Mutations in Turkish Children with Isolated Growth Hormone Deficiency
OBJECTIVE Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of GH or lack of GH action. Mutations in the gene encoding for GH-releasing hormone receptor (GHRHR) have been detected in patients with IGHD type IB. However, genetic defects on GHRHR causing IGHD in the Turkish population have not yet been reporte...
متن کاملPrimary growth hormone insensitivity and psychomotor delay
We report a case of short stature irresponsive to growth hormone (GH) replacement therapy. Low GH response to provocative tests and undetectable IGF-1 levels had suggested GH deficiency, while response to therapy indicated GH insensitivity. Molecular evaluation of the GH/IGF-1 axis should be performed in these cases to improve diagnosis and therapy.
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ژورنال
عنوان ژورنال: The Journal of Clinical Endocrinology and Metabolism
سال: 2021
ISSN: ['1945-7197', '0021-972X']
DOI: https://doi.org/10.1210/clinem/dgab550