Hasani-Ranjbar Shirin, Jouyandeh Zahra, Amoli Mahsa Mohammad, Soltani Akbar, Arzaghi Seyed Masoud
Obesity & Eating Habits Research Center, Endocrinology and metabolism Cellular & Molecular Science Institute, Endocrinology & Metabolism research institute, Tehran University of Medical Sciences, Tehran, Iran ; Endocrinology and Metabolism Research center, Endocrinology & Metabolism research institute, Tehran University of Medical Sciences, Tehran, Iran ; Endocrinology & Metabolism Research Institute, 5th Floor, Shariati Hospital, North Kargar Ave., Tehran 14114, Iran.
Endocrinology and Metabolism Research center, Endocrinology & Metabolism research institute, Tehran University of Medical Sciences, Tehran, Iran.
J Diabetes Metab Disord. 2014 May 22;13:56. doi: 10.1186/2251-6581-13-56. eCollection 2014.
Pseudohypoparathyroidism(PHP) is a heterogeneous group of rare metabolic disorders characterized by hypocalcemia and hyperphosphatemia resulting from PTH resistance. Different forms of PHP have been reported based on biochemical and clinical manifestation and genetic findings. Most of these forms are caused by defects in GNAS, an imprinted gene locus with multiple subunits. We reported a 12- year- old girl with unusual clinical manifestations of Pseudopseudohypoparathyroidism(PPHP).
After clinical and biochemical evaluations, the patients' genomic DNA was isolated from peripheral blood leukocytes using salting out method. The whole coding sequences of GNAS gene including 13 exons were amplified by PCR. Quantitative PCR reactions were performed too.
We described a 12- year- old girl with Albright Hereditory osteodystrophy (AHO) phenotype, poor school performance, some abnormal movements, TSH resistance with normal serum calcium and phosphorus levels and normal Gsα bioactivity with no mutation in GNAS exons. Unusual neuropsychiatric findings in this patient were compatible with Asperger syndrome.
According to our findings this patient could not be categorized in any of PHP subgroups. Identifying of such individuals may be useful to discover different genetic patterns in pseudohypoparathyroidism and pseudopseudohypoparathyroidism. It is important to identify patients in whom PHP is caused by novel GNAS mutations, as careful investigations of these findings will likely further our knowledge of this complex and this unique disorder. In addition this case presented with unusual neuropsychiatric findings which has not been reported up to now.
假性甲状旁腺功能减退症（PHP）是一组罕见的异质性代谢紊乱疾病，其特征为甲状旁腺激素抵抗导致的低钙血症和高磷血症。根据生化、临床表现及基因检测结果，已报道了不同类型的PHP。这些类型中的大多数是由GNAS缺陷引起的，GNAS是一个具有多个亚基的印记基因座。我们报告了一名患有假性假性甲状旁腺功能减退症（PPHP）不寻常临床表现的12岁女孩。
经过临床和生化评估后，采用盐析法从外周血白细胞中分离患者的基因组DNA。通过聚合酶链反应（PCR）扩增包括13个外显子的GNAS基因的完整编码序列。同时也进行了定量PCR反应。
我们描述了一名12岁女孩，具有奥尔布赖特遗传性骨营养不良（AHO）表型、学业成绩差、一些异常动作、促甲状腺激素抵抗，血清钙和磷水平正常，Gsα生物活性正常，GNAS外显子无突变。该患者不寻常的神经精神表现与阿斯伯格综合征相符。
根据我们的研究结果，该患者无法归类于任何PHP亚组。识别此类个体可能有助于发现假性甲状旁腺功能减退症和假性假性甲状旁腺功能减退症的不同遗传模式。识别由新的GNAS突变引起PHP的患者很重要，因为对这些结果的仔细研究可能会进一步加深我们对这种复杂独特疾病的认识。此外，该病例呈现出迄今为止尚未报道的不寻常神经精神表现。
