• Clinical and Experimental Pediatrics
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• 제46권10호
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• pp.1032-1035
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• 2003

저자들은 미숙아에서 이학적 검사상 AHO를 동반하지 않고, 생화학 검사에서는 저칼슘혈증, 고인산혈증, 혈청 PTH의 증가와 24시간 소변의 기저 cAMP의 증가를 보이면서, 대퇴골의 자발골절을 동반했던 가성부갑성선 기능저하증 1례를 문헌 고찰과 함께 보고하는 바이다.

• Journal of Interdisciplinary Genomics
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• 제5권2호
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• pp.29-31
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• 2023

Pseudohypoparathyroidism (PHP) is very rare and shows heterogeneity with impaired genetic components. PHP is characterized by parathyroid hormone resistance to target organ, related with a GNAS (guanine nucleotide-binding protein α-subunit) mutation and epimutation. PHP receptor is coupled with the stimulatory G protein which activates cyclic adenosine monophosphate formation. PHP type 1A is caused by inactivating mutations on the maternal allele of the GNAS whereas paternal allele mutations cause pseudopseudohypoparathyroidism. PHP type 1B is caused by abnormal patterns of methylation in differentially methylated region which can be divided into partial or complete. This disease has some difficulties to diagnose according to these different molecular alterations caused by complex genetic and epigenetic defects. According to this different molecular alterations, genetic confirmation must be done to discriminate their etiology.

• 대한유전성대사질환학회지
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• 제20권2호
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• pp.44-49
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• 2020

가성부갑상샘기능저하증(pseudohypoparathyroidism, PHP)은 부갑상샘호르몬에 대해 표적 기관이 저항성을 가지며, 저칼슘혈증과 고인산혈증을 특징으로 하는 질병이다. PHP의 원인은 자극형 G 단백의 신호전달이 문제인데, α-아형을 인코딩하는 GNAS 유전자와 GNAS 유전자 상부의 각인 이상으로 발생한다. 가족력 없이 발생하는 산발성 PHP 1b형은 GNAS 유전자 상류 다발 지역의 메칠화 이상으로, 그 중 일부는 모계 유전형이 소실되고, 부계 유전형만이 표현된다. 본 논문에서는 간헐적 강직을 주소로 내원한 10.8세 남아에서 발생한 20번 염색체 장완의 부계 단친성 이염색체에 의한 산발성 PHP 1b형의 증례를 고찰해보고자 한다.

• Clinical and Experimental Pediatrics
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• 제57권5호
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• pp.240-244
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• 2014

Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 ($p.Gln213^*$). To our knowledge, this is a novel mutation in GNAS.

• Journal of Genetic Medicine
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• 제14권1호
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• pp.18-22
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• 2017

Pseudohypoparathyroidism type 1b (PHP 1b) is the result of end organ resistance to parathyroid hormone (PTH) in the absence of any features of Albright's hereditary osteodystrophy. There are two subtypes of PHP 1b with different genetic mechanisms. One subtype is related to a maternally derived 3kb microdeletion involving STX 16 gene, and is inherited in an autosomal dominant mode. Familial autosomal dominant inheritance of PHP 1b is relatively rare. The other subtype is associated with more extensive loss of imprinting at the GNAS locus that affects at least one additional differential methylated (hypermethylation at neuroendocrine secretory protein and hypomethylation at antisense transcript and or extra-large stimulatory G protein region) without microdeletion of the STX 16 or AS gene. It can be sporadic due to an imprinting defect in the GNAS gene. In our case, an 8-year-old girl was referred for suspected PHP with no feature of Albright hereditary osteodystrophy. Blood test results revealed hypocalcemia and hyperphosphatemia. Elevated PTH was also checked. There was no family history of endocrine or developmental problem. Her intelligence was normal, but she had inferior sociability at that time. Based on above, we diagnosed a rare case of paternal uniparental disomy of the long arm of chromosome 20 as the cause of PHP 1b by microsatellite marker test of chromosome 20.

• Laboratory Medicine Online
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• 제7권2호
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• pp.83-87
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• 2017

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein ($Gs{\alpha}$). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.