An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism

Bowl, Michael R.; Nesbit, M. Andrew; Harding, Brian; Levy, Elaine R.; Jefferson, Ann; Volpi, Emanuela V.; Rizzoti, Karine; Lovell-Badge, Robin; Schlessinger, David; Whyte, Michael P.; Thakker, Rajesh V.

doi:10.1172/jci24156

Cited by 135 publications

(82 citation statements)

References 48 publications

(126 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed PA3 defects, albeit with less penetrance and severity. We did not, however, see defects in the early parathyroid/thymus primordia, even though human patients with a translocation breakpoint upstream of SOX3 are affected by hypoparathyroidism (Bowl et al, 2005). This may reflect a role for SOX3 during subsequent development of this gland, in which its expression is maintained.…”

Section: Discussioncontrasting

confidence: 65%

SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis

Rizzoti¹,

Lovell-Badge²

2007

Development

Self Cite

View full text Add to dashboard Cite

Craniofacial development is a complex multi-step process leading to the morphogenesis of the face and sense organs, and to that of the neck, including the anteriormost part of the respiratory and digestive apparatus and associated endocrine glands. In vertebrates, the process is initiated by the formation of the pharyngeal arches from ectoderm, endoderm and mesoderm. These arches are then populated by neural crest cells, which originate from the central nervous system. We show here that, in mouse, there is a requirement for the HMG box factor SOX3 during the earliest stage of pharyngeal development: the formation of the pharyngeal pouches that segment the pharyngeal region by individualising each arch. In Sox3-null mutants, these pouches are expanded at the detriment of the second pharyngeal arch. As a consequence, neural crest cell migration and ectoderm-derived epibranchial placode development are affected, leading to craniofacial defects. We also show that Sox3 genetically interacts both with FgfR1 and with Sox2, another member of the Soxb1 family, to fulfil its function in the pharyngeal region. Although the importance of the neural crest has long been recognised, our studies highlight the equally crucial role of the pharyngeal region in craniofacial morphogenesis. They also give insight into the formation of pharyngeal pouches, of which little is known in vertebrates. Finally, this work introduces two new players in craniofacial development -SOX3 and SOX2.

show abstract

Section: Discussioncontrasting

confidence: 65%

SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis

Rizzoti¹,

Lovell-Badge²

2007

Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…The variability in phenotypic expression of heterozygous mutation may be conditioned by polygenic mechanism or by environmental factors (57,58). Among the polygenic factors, possibilities include mutations in the parathyroid glandrelated transcription factor proteins other than GCM2 such as PAX1, PAX9, GATA3, Hoxa3, TBX1, and SOX3 (6,9,(59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

“…Hypoparathyroidism is a heterogeneous group of disorders characterized by tetany, cataract, basal ganglia calcification, hypocalcemia, hyperphosphatemia, and subnormal serum parathyroid hormone (PTH) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Recently, Dolores Shoback has classified its pathophysiologic mechanisms into three broad categories (13).…”

Section: Introductionmentioning

confidence: 99%

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

Tomar¹,

Bora²,

Singh³

et al. 2010

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Glial cells missing 2 (GCM2) gene encodes a parathyroid-specific transcription factor. We assessed GCM2 gene sequence in patients with isolated hypoparathyroidism (IH). Design: Case-control study. Methods: Complete DNA sequencing of the GCM2 gene including its exons, promoter, and 5 0 and 3 0UTRs was performed in 24/101 patients with IH. PCR-restriction fragment length polymorphism was used to detect a novel R110W mutation in all 101 IH patients and 655 healthy controls. Significance of the mutation was assessed by electrophoretic mobility shift assay (EMSA) and nuclear localization on transfection.Results: A heterozygous R110W mutation was present in DNA-binding domain in 11/101 patients (10.9%) and absent in 655 controls (P!10 K7 ). Four of 13 nonaffected first-degree relatives for five of these index cases had R110W mutation. Four heterozygous single nucleotide polymorphisms were found in the 5 0 region. One of the 11 patients with R110W also had T370M change in compound heterozygous form. Mutant R110W and T370M GCM2 proteins showed decreased binding with GCM recognition elements on EMSA indicating loss of function. Both wild-type and R110W mutant GCM2 proteins showed nuclear localization. Conclusions: The present study indicates a significant association of R110W variant with IH. Absence of effect of heterozygous R110W mutation on DNA binding and presence of the same mutation in asymptomatic family members indicate that additional genetic (akin to T370M change) or nongenetic factors might contribute to the expression of diseases in IH. Alternatively, it is possible that association of R110W with IH could be due to linkage disequilibrium with the unidentified relevant genes in IH.

show abstract

“…Thus, mutations in this gene seem to result in congenital hypoparathyroidism [33][34][35]. Sry-Box 3 (SOX3) gene is a candidate for X-linked recessive hypoparathyroidism, but this has not been definitely proven [36].…”

Section: Pathogenesis and Differential Diagnosis Of Hypocalcemia (Figmentioning

confidence: 99%

Causes and Differential Diagnosis of Hypocalcemia -Recommendation Proposed by Expert Panel Supported by Ministry of Health, Labour and Welfare, Japan-

Fukumoto

Namba²,

Ozono³

et al. 2008

Endocr J

View full text Add to dashboard Cite

Abstract. Serum calcium (Ca) level is maintained within a narrow range mainly by actions of parathyroid hormone (PTH) and 1,25-dihydroxyvitmain D [1,25(OH) 2 D]. While it is not rare to encounter hypocalcemia in clinical practice, there is currently no practical guideline for the differential diagnosis of hypocalcemia. We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many genetic or other causes have been identified recently. Hypocalcemia can be divided into two categories, hypocalcemia with low serum phosphate level, and one with normal to elevated serum phosphate level. Deficient actions of 1,25(OH) 2 D, loss of Ca into urine, and deposition of Ca in bone or soft tissues are main causes of hypocalcemia with low to low normal serum phosphate level. Hypocalcemia with high normal to high serum phosphate level includes chronic renal failure and hypoparathyroidism. Hypoparathyroidism is subdivided into PTH-deficient hypoparathyroidism and pseudohypoparathyroidism. Recent investigations identified several causes of PTH-deficient hypoparathyroidism, including genetic abnormalities and parathyroid autoantibodies, which should be differentiated from idiopathic hypoparathyroidism. Physical and laboratory findings, the time of the onset of diseases and accompanying illness can be clues for identifying causes of PTH-deficient hypoparathyroidism.

show abstract

An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism

Abstract: X-linked recessive hypoparathyroidism, due to parathyroid agenesis, has been mapped to a 906-kb region on Xq27 that contains 3 genes (ATP11C, U7snRNA, and SOX3), and analyses have not revealed mutations. We

Cited by 135 publications

References 48 publications

SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis

SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members

Causes and Differential Diagnosis of Hypocalcemia -Recommendation Proposed by Expert Panel Supported by Ministry of Health, Labour and Welfare, Japan-

Contact Info

Product

Resources

About