Endocrinology and Metabolism

Original Article

Miscellaneous
Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism: Jihong Bae, Hong Seok Choi, So Young Park, Do-Eun Lee, Sihoon Lee; Endocrinol Metab. 2018;33(2):252-259. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.252

5,249 View
70 Download
10 Web of Science
9 Crossref

Background

Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family.

Methods

Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control.

Results

We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained.

Conclusion

Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

Citations

Citations to this article as recorded by

A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature
Jian Sun, Nian Yang, Zhengquan Xu, Hongbo Cheng, Xiangxin Zhang
Molecular Genetics & Genomic Medicine.2024;[Epub] CrossRef
A novel mutation in PTHLH in a family with a variable phenotype with brachydactyly, short stature, oligodontia and developmental delay
Mirjam E.A. Scheffer-Rath, Hermine E. Veenstra-Knol, Annemieke M. Boot
Bone Reports.2023; 19: 101699. CrossRef
Bioactive phytoconstituents as potent inhibitors of casein kinase-2: dual implications in cancer and COVID-19 therapeutics
Farah Anjum, Md Nayab Sulaimani, Alaa Shafie, Taj Mohammad, Ghulam Md. Ashraf, Anwar L. Bilgrami, Fahad A. Alhumaydhi, Suliman A. Alsagaby, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
RSC Advances.2022; 12(13): 7872. CrossRef
Characterization and expression profiling of G protein-coupled receptors (GPCRs) in Spodoptera litura (Lepidoptera: Noctuidae)
Yanxiao Li, Han Gao, Hui Zhang, Runnan Yu, Fan Feng, Jing Tang, Bin Li
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics.2022; 44: 101018. CrossRef
Genes with specificity for expression in the round cell layer of the growth plate are enriched in genomewide association study (GWAS) of human height
Nora E. Renthal, Priyanka Nakka, John M. Baronas, Henry M. Kronenberg, Joel N. Hirschhorn
Journal of Bone and Mineral Research.2020; 36(12): 2300. CrossRef
Search for Novel Mutational Targets in Human Endocrine Diseases
So Young Park, Myeong Han Seo, Sihoon Lee
Endocrinology and Metabolism.2019; 34(1): 23. CrossRef
A Heterozygous Splice-Site Mutation in PTHLH Causes Autosomal Dominant Shortening of Metacarpals and Metatarsals
Monica Reyes, Bert Bravenboer, Harald Jüppner
Journal of Bone and Mineral Research.2019; 34(3): 482. CrossRef
A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum
Jia Huang, Hong-Yan Liu, Rong-Rong Wang, Hai Xiao, Dong Wu, Tao Li, Ying-Hai Jiang, Xue Zhang
Chinese Medical Journal.2019; 132(14): 1681. CrossRef
Parathyroid Hormone-Related Protein in the Hand or Out of Hand?
Sang Wan Kim
Endocrinology and Metabolism.2018; 33(2): 202. CrossRef

Case Reports

A Case of Pseudohypoparathyroidism with Graves' Disease.: Gil Woo Lee, Jae Hoon Kim, Kang Won Lee, Sa Il Kim, Sang Mo Hong, Dong Sun Kim, Woong Hwan Choi, You Hern Ahn, Tae Wha Kim; Endocrinol Metab. 2010;25(3):221-225. Published online September 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.3.221

1,875 View
29 Download

Abstract PDF: Pseudohypoparathyroidism is a rare disease that is characterized by target cell resistance to the effects of parathyroid hormone and this disease is classified into various types depending on the phenotypic and biochemical findings. The patients with pseudohypoparathyroidism present with the clinical and biochemical features of hypoparathyroidism, but they have an increased serum level of parathyroid hormone. We experienced a case of pseudohypoparathyroidism in a 24 years old woman who had Graves' disease at that time. She had hypocalcemia, hyperphosphatemia, an elevated serum parathyroid hormone level and a normal urinary basal cyclic AMP(adenosine monophosphate) level. She also had a normal phenotypic appearance. Therefore, she was classified as suffering with pseudohypoparathyroidism type II. The clinical and laboratory abnormalities were improved by calcium supplementation in addition to vitamin D. To the best of our knowledge, this is the first case of pseudohypoparathyroidism combined with Graves' disease in Korea.

A Case of Pseudohypoparathyroidism Worsened by Rhabdomyolysis.: Won Jun Kim, Sin Je Moon, Hye Young Kim, Chang Beom Lee; J Korean Endocr Soc. 2009;24(3):195-200. Published online September 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.3.195

2,324 View
26 Download
1 Crossref

Abstract PDF

The term pseudohypoparathyroidism describes a rare disorder characterized by resistance to the action of immunoreactive parathyroid hormone (PTH) in peripheral tissue rather than a deficiency of PTH. Patients present with tetany, spasm, hypocalcemia, hyperphosphatemia, and Albright's hereditary osteodystrophy (AHO). We present a case of symptomatic hypocalcemia due to pseudohypoparathyroidism aggravated by rhabdomyolysis. A 21-year-old man presented with tetany, AHO phenotypes and an ankle infection. Rhabdomyolysis was confirmed by marked elevation of serum creatine phosphokinase, more than 10 times above normal. Spasm was observed and the serum value of total calcium was as low as 3.7 mg/dL and that of phosphate was as high as 7.0 mg/dL, and the peak level of PTH was at 80.4 pg/mL. Although not surveyed by Ellsworth-Howard test and molecular study, it was classified as pseudohypoparathyroidism type 1a or 1c. The clinical and laboratory abnormalities were corrected by vitamin D in addition to calcium. The patient's mother, sister, and grandmother had AHO phenotypes without clinical and biochemical manifestations. To the best of our knowledge, this is the first case by maternal inheritance that AHO phenotypes appear for three generations of a family in Korea.

Citations

Citations to this article as recorded by

A Case of Pseudohypoparathyroidism with Graves' Disease
Gil Woo Lee, Jae Hoon Kim, Kang Won Lee, Sa Il Kim, Sang Mo Hong, Dong Sun Kim, Woong Hwan Choi, You Hern Ahn, Tae Wha Kim
Endocrinology and Metabolism.2010; 25(3): 221. CrossRef

A Case of Pseudopseudohypoparathyroidism with Normal Stature.: Sae Rom Kim, Yun Jeong Doh, Hee Kyung Kim, Seong Su Moon, Ju Young Lee, Jae Han Jeon, Soo Won Kim, Bo Wan Kim, In Kyu Lee, Jung Guk Kim; J Korean Endocr Soc. 2009;24(2):138-143. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.138

2,298 View
33 Download
1 Crossref

Abstract PDF

Pseudopseudohypoparathyroidism (PPHP) is characterized by the phenotype of Albright hereditary osteodystrophy (AHO) alone without biochemical evidence of multihormone resistance, which is unlike pseudohypoparathyroidism. AHO is associated with characteristic developmental abnormalities that include a short stocky stature, a short neck, brachydactyly, a round face, central obesity, mental retardation and subcutaneous ossifications. AHO is an autosomal dominant disease that's caused by heterozygous inactivating mutations in the Gsalpha gene (GNAS1). Melanocortin-4 receptor (MC4R) is a hypothalamic Gs-coupled receptor that is thought to mediate the central effect of leptin on satiety. MC4R mutations cause morbid obesity starting in infancy, as well as an elevated leptin level. A 62 year old man with a height of 171.5 cm, a round face, a short neck, central obesity and brachydactyly had normal ranges of serum calcium, phosphorus and PTH and a normal Ellsworth-Howard test. GNAS1 gene analysis revealed substitution of alanine to cysteine in the 165 codon of exon 6 and substitution of alanine to cysteine in the 231 codon of exon 9. Two known SNPs (Cyt-1042Thy, Gua-719Ade) in the MC4R were detected in the patient. We report here on a case of PPHP and the patient had normal stature. We propose that MC4R may have contributed to the obesity & normal stature of this patient.

Citations

Citations to this article as recorded by

Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism
Sang Jin Kim, Sang-Yoon Kim, Han-Byul Kim, Hyukwon Chang, Ho-Chan Cho
Endocrinology and Metabolism.2013; 28(3): 236. CrossRef

A Case of Pseudohypoparathyroidism without Albright's Hereditary Osteodystrophy in an Adult.: Yoonbum Lee, Jungmin Roh, Jeong seon Yoo, Jeongwoo Han, Jisun Nam, Minho Cho, Jongsuk Park, Chulwoo Ahn, Kyungrae Kim; J Korean Endocr Soc. 2009;24(2):132-137. Published online June 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.2.132

2,086 View
26 Download
1 Crossref

Abstract PDF

Pseudohypoparathyroidism is a rare disease caused by resistance to parathyroid hormone, and is associated with typical clinical typical symptoms such as tetany and seizures, hypocalcemia, hyperphosphatemia and increased parathyroid hormone levels. Pseudohypoparathyroidism is classified to Type Ia, Ib, Ic and II according to the clinical and biochemical manifestations. Type Ia and Ic have morphological characteristics called Albright's hereditary osteodystrophy. Type Ib differs from type II for the pathogenesis. Type Ib may~receptors and type II may~ pathway, but the pathophysiology of type II is not clear yet. Administration of parathyroid hormone extract may help to distinguish between the two types. We report a case of a pseudohypoparathyroidism type Ib or II patient who had tetany, hypocalcemia and hyperphosphatemia with normal morphologic features.

Citations

Citations to this article as recorded by

A Case of Pseudohypoparathyroidism with Graves' Disease
Gil Woo Lee, Jae Hoon Kim, Kang Won Lee, Sa Il Kim, Sang Mo Hong, Dong Sun Kim, Woong Hwan Choi, You Hern Ahn, Tae Wha Kim
Endocrinology and Metabolism.2010; 25(3): 221. CrossRef

A Case of Pseudopseudohypoparathyroidism with Partial Empty Sella.: Jang Hyun Koh, Yeon Lee, Joung Wook Choi, Tae Won Hong, Mi Jin Kim, Young Goo Shin, Choon Hee Chung; J Korean Endocr Soc. 2004;19(4):433-438. Published online August 1, 2004

1,170 View
19 Download

Abstract PDF: Pseudohypoparathyroidism (PHP) is a rare endocrine syndrome, which is characterized by Albright's hereditary osteodystrophy (AHO). Pseudopseudohypoparathyroidism (PPHP) presents with AHO features, but does not show clinical symptoms or the same laboratory finding as hypoparathyroidism. A 54 aged woman visited our department with lower abdominal pain. She had a history of a total hysterectomy due to persistent uterine bleeding 30 years previously. She showed abnormal physical findings, including a round face, short stature and brachydactyly. Her hormonal data were within normal limits, as follows: PTH 40.72 pg/mL, calcium 8.6 mg/dL, phosphorus 4.0 mg/dL and 24 hour urine cAMP 3.2 nmol/mg. On a pituitary challenge test, the basal levels and response rates of FSH and LH were low, and a sella CT scan showed partially empty sella. Herein is reported a case of PPHP, with partial empty sella, with a review of the literature

First
Prev
Page of 1
Next
Last

Search