scholarly journals Intronic variant in POU1F1 associated with canine pituitary dwarfism

2021 ◽  
Author(s):  
Kaisa Kyöstilä ◽  
Julia E. Niskanen ◽  
Meharji Arumilli ◽  
Jonas Donner ◽  
Marjo K. Hytönen ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Low Frequency ◽  
Canine Model ◽  
Abnormal Development ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Genome Wide ◽  
Fourth Exon ◽  
Related Breed ◽  
Generation Sequencing

AbstractThe anterior pituitary gland secretes several endocrine hormones, essential for growth, reproduction and other basic physiological functions. Abnormal development or function of the pituitary gland leads to isolated or combined pituitary hormone deficiency (CPHD). At least 30 genes have been associated with human CPHD, including many transcription factors, such as POU1F1. CPHD occurs spontaneously also in mice and dogs. Two affected breeds have been reported in dogs: German Shepherds with a splice defect in the LHX3 gene and Karelian Bear Dogs (KBD) with an unknown genetic cause. We obtained samples from five KBDs presenting dwarfism and abnormal coats. A combined analysis of genome-wide association and next-generation sequencing mapped the disease to a region in chromosome 31 and identified a homozygous intronic variant in the fourth exon of the POU1F1 gene in the affected dogs. The identified variant, c.605-3C>A, resided in the splice region and was predicted to affect splicing. The variant's screening in three new prospective cases, related breeds, and ~ 8000 dogs from 207 breeds indicated complete segregation in KBDs with a carrier frequency of 8%, and high breed-specificity as carriers were found at a low frequency only in Lapponian Herders, a related breed. Our study establishes a novel canine model for CPHD with a candidate POU1F1 defect.

scholarly journals Detection of genome-wide low-frequency mutations with Paired-End and Complementary Consensus Sequencing (PECC-Seq) revealed end-repair derived artifacts as residual errors

2019 ◽  
Author(s):  
Xinyue You ◽  
Suresh Thiruppathi ◽  
Weiying Liu ◽  
Yiyi Cao ◽  
Mikihiko Naito ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Low Frequency ◽  
Repair Process ◽  
Sequencing Error ◽  
Base Substitution ◽  
Next Generation ◽  
Background Error ◽  
Technical Errors ◽  
Genome Wide ◽  
Generation Sequencing

ABSTRACTTo improve the accuracy and the cost-efficiency of next-generation sequencing in ultralow-frequency mutation detection, we developed the Paired-End and Complementary Consensus Sequencing (PECC-Seq), a PCR-free duplex consensus sequencing approach. PECC-Seq employed shear points as endogenous barcodes to identify consensus sequences from the overlap in the shortened, complementary DNA strands-derived paired-end reads for sequencing error correction. With the high accuracy of PECC-Seq, we identified the characteristic base substitution errors introduced by the end-repair process of mechanical fragmentation-based library preparations, which were prominent at the terminal 6 bp of the library fragments in the 5’-NpCpA-3’ or 5’-NpCpT-3’ trinucleotide context. As demonstrated at the human genome scale (TK6 cells), after removing these potential end-repair artifacts from the terminal 6 bp, PECC-Seq could reduce the sequencing error frequency to mid-10−7 with a relatively low sequencing depth. For TA base pairs, the background error rate could be suppressed to mid-10−8. In mutagen-treated TK6, slight increases in mutagen treatment-related mutant frequencies could be detected, indicating the potential of PECC-Seq in detecting genome-wide ultra-rare mutations. In addition, our finding on the patterns of end-repair artifacts may provide new insights in further reducing technical errors not only for PECC-Seq, but also for other next-generation sequencing techniques.

scholarly journals Evaluation of pituitary imaging in patients with PROP-1 gene mutation

Medicina ◽  
2009 ◽  
Vol 45 (9) ◽  
pp. 693 ◽  
Author(s):  
Natalija Tkačenko ◽  
Danutė Lašienė ◽  
Silvija Jakštienė ◽  
Algidas Basevičius ◽  
Rasa Verkauskienė
Keyword(s):  
Transcription Factor ◽  
Pituitary Gland ◽  
Gene Mutation ◽  
Anterior Pituitary ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Imaging Studies ◽  
Pituitary Hyperplasia ◽  
Pituitary Hypoplasia ◽  
Genetically Determined

The most common genetically determined cause of multiple pituitary hormone deficiency is PROP-1 gene mutation. PROP-1 is a transcription factor involved in the development of pituitary gland and affects hormonal synthesis of anterior pituitary. The aim of our study was to evaluate radiological aspects of the pituitary region in patients with PROP-1 gene mutation. Pituitary imaging studies were performed in 12 patients with a confirmed PROP-1 gene mutation. Pituitary hyperplasia was found in 5 (42%) and pituitary hypoplasia in 4 (33%) patients. Changes in pituitary size were not associated with the type of PROP-1 gene mutation.

Genetic Anomalies of Growth Hormone Deficiency in Pediatrics

2020 ◽  
Vol 20 ◽  
Author(s):  
Majid Firouzi ◽  
Hamidreza Sherkatolabbasieh ◽  
Shiva Shafizadeh
Keyword(s):  
Growth Hormone ◽  
Pituitary Gland ◽  
Growth Hormone Deficiency ◽  
Early Treatment ◽  
Hormone Deficiency ◽  
Genetic Defects ◽  
Pituitary Hormone ◽  
Deficiency Disease ◽  
Complex Genetics ◽  
Future Consequences

: Several different proteins regulate, directly or indirectly, the production of growth hormone from the pituitary gland, thereby complex genetics is involved. Defects in these genes are related to growth hormone deficiency solely, or deficiency of other hormones, secreted from the pituitary gland including growth hormone. These studies can aid clinicians to trace the pattern of the disease between the families, start early treatment and predict possible future consequences. This paper highlights some of the most common and novel genetic anomalies concerning growth hormone, which are responsible for various genetic defects in isolated growth and combined pituitary hormone deficiency disease.

scholarly journals Evolving pituitary hormone deficits in primarily isolated GHD: a review and experts’ consensus

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Gerhard Binder ◽  
Dirk Schnabel ◽  
Thomas Reinehr ◽  
Roland Pfäffle ◽  
Helmuth-Günther Dörr ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Current Knowledge ◽  
Serum Insulin ◽  
Growth Failure ◽  
Endocrine Function ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Hypothalamic Region ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency

Abstract Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained. There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.

scholarly journals SAT-288 Pituitary Developmental Defects Caused by Haploinsufficiency for the Transcription Factor SIX3 Are Worsened by POU1F1 Deficiency

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Michelle Brinkmeier ◽  
Sally Ann Camper
Keyword(s):  
Transcription Factor ◽  
Pituitary Gland ◽  
Clinical Features ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Loss Of Function ◽  
Pituitary Hormone Deficiency ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Vasopressin Neurons

Abstract Advances in genomic technologies are revolutionizing the practice of medicine by delivering molecular diagnoses that can be informative for prognosis and treatment of genetic disorders. Most of the known genetic causes of multiple pituitary hormone deficiency have been investigated as monogenic disorders. It can be challenging to predict clinical features from genetic data, as loss of function mutations in some genes can present with a spectrum of phenotypes ranging from craniofacial abnormalities, intellectual disability, and neurosensory and neuroendocrine defects to pituitary hormone deficiency with no other abnormalities. Although maternal exposures could be contributing factors, the contribution of rare, deleterious variation in other genes is a likely contributor. In humans, loss of function mutations in the transcription factor SIX3 cause variable, autosomal dominant holoprosencephaly with incomplete penetrance, and mouse models recapitulate some of the clinical features. Because Six3 and Pou1f1 gene expression patterns overlap in pituitary development, we hypothesized that doubly heterozygous mice (Six3+/-; Pou1f1+/dw) might have pituitary anomalies not present in singly heterozygous mice. We intercrossed Six3+/- and Pou1f1+/dw mice to produce doubly heterozygous animals. At e11.5, both Six3+/- and Six3+/-; Pou1f1+/dw exhibited abnormal morphology of the developing infundibulum and Rathke’s pouch, although ventral diencephalon expression of Tle4, Fgf10, and Nkx2.1 appeared normal. Both newborn Six3+/- and Six3+/-; Pou1f1+/dw littermates had abnormal pituitary gland morphology that resembled that of Aes-/-. AES is a co-repressor that interacts with SIX3. Specification of vasopressin neurons and anterior lobe hormone cell types appeared normal. Mice of all genotypes were born in expected Mendelian ratios (N=144, p=0.49), and there were no significant differences in body weight at 3 wks. A portion of the Six3+/- and doubly heterozygous mice developed hydrocephalus, exhibited failure to thrive, and died (6-9% of N=82, 85, respectively). At 6 wks, 25% (N=61) of the Six3+/-; Pou1f1+/dw animals exhibited striking pituitary dysmorphology in which the rostral aspect of the pituitary penetrated the palate. This was not observed in single heterozygotes. These results reveal that haploinsufficiency for Six3 affects Rathke’s pouch formation, resulting in pituitary gland dysmorphology in and around the stem cell niche. A significant portion of the Six3+/-; Pou1f1+/dw doubly heterozygous mice have a more pronounced pituitary phenotype than Six3+/-, supporting the possibility of digenic pituitary disease and highlighting phenotypic variability. Genetically engineered mice provide an excellent tool for assessing the possibility of gene-gene interactions that could enhance the severity of hypopituitarism and associated craniofacial development.

scholarly journals Growth Hormone Deficiency in Children and Adult Patients with Hypopituitarism: Challenges in the Diagnosis and Management

2017 ◽  
Vol 1 (1) ◽  
pp. 01-04
Author(s):  
Mansour Hosseinlou
Keyword(s):  
Growth Hormone ◽  
Pituitary Gland ◽  
Growth Hormone Deficiency ◽  
Medical Condition ◽  
Pituitary Hormones ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Diagnosis And Management ◽  
Treatment Regimens

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used. Hypopituitarism is a complex medical condition associated with increased morbidity and mortality, requires complicated treatment regimens, and necessitates lifelong follow up by the endocrinologist.

scholarly journals Guidelines for patients with the hypothalamo-pituitary disorders; School for patients

1996 ◽  
Vol 42 (5) ◽  
pp. 32-33
Author(s):  
G. A. Melnichenko ◽  
T. I. Romantsova ◽  
V. A. Chernogolov ◽  
M. G. Pavlova
Keyword(s):  
Pituitary Gland ◽  
Head Injuries ◽  
Pituitary Hormones ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Common Symptom ◽  
General Weakness ◽  
Direct Pressure ◽  
Principles Of Treatment ◽  
Healthy Part

In the previous issue, we talked about the structure and functions of the hypothalamic-pituitary system, as well as the need to create schools to help patients with hypothalamic-pituitary disorders. Today we want to focus on the manifestations of pituitary hormone deficiency and the basic principles of treatment of this pathology. Lack of pituitary hormones If the pituitary gland does not produce certain hormones or produces them in small quantities, then this condition is called hypopituitarism. Most often, this condition occurs due to the presence of a benign (i.e., non-cancerous) tumor of the pituitary gland or hypothalamus. If a person has a pituitary tumor, it can lead to a decrease in its functions by direct pressure of the tumor mass on the healthy part of the pituitary gland or as a result of surgical treatment or irradiation of the tumor. Less commonly, hypopituitarism is caused by infectious diseases of the brain (such as meningitis), significant blood loss (for example, during childbirth), head injuries, as well as rare diseases (sarcoidosis, etc.). I. Lack of ACTH. 1. What are the symptoms of ACTH deficiency? The most common symptom is fatigue, a feeling of general weakness, sometimes dizziness. Some patients have nausea and diarrhea.

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