Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency

Budny, Bartłomiej; Karmelita‐Katulska, Katarzyna; Stajgis, Marek; Żemojtel, Tomasz; Ruchała, Marek; Ziemnicka, Katarzyna

doi:10.3390/ijms21165757

Cited by 10 publications

(10 citation statements)

References 37 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The possibility cannot be ruled out that monogenetic diseases and oligogenic abnormalities may be associated with the disease ( 65 ). Moreover, the results of a recent study revealed copy-number variants in several genes that might contribute to the formation of CPHD ( 66 ).…”

Section: Discussionmentioning

confidence: 99%

Novel genes and variants associated with congenital pituitary hormone deficiency in the era of next-generation sequencing

et al. 2022

View full text Add to dashboard Cite

Combined pituitary hormone deficiency (CPHD) is not a rare disorder, with a frequency of approximately 1 case per 4,000 live births. However, in most cases, a genetic diagnosis is not available. Furthermore, the diagnosis is challenging because no clear correlation exists between the pituitary hormones affected and the gene(s) responsible for the disorder. Next-generation sequencing (NGS) has recently been widely used to identify novel genes that cause (or putatively cause) CPHD. This review outlines causative genes for CPHD that have been newly reported in recent years. Moreover, novel variants of known CPHD-related genes (POU1F1 and GH1 genes) that contribute to CPHD through unique mechanisms are also discussed in this review. From a clinical perspective, variants in some of the recently identified causative genes result in extra-pituitary phenotypes. Clinical research on the related symptoms and basic research on pituitary formation may help in inferring the causative gene(s) of CPHD. Future NGS analysis of a large number of CPHD cases may reveal new genes related to pituitary development. Clarifying the causative genes of CPHD may help to understand the process of pituitary development. We hope that future innovations will lead to the identification of genes responsible for CPHD and pituitary development.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel genes and variants associated with congenital pituitary hormone deficiency in the era of next-generation sequencing

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Lhx4 is critical to pituitary development 43 , 44 . Besides, the mutation of human LHX4 is usually associated with CPHD (characterized by a deficiency of the growth hormone and growth retardation) 32 , 45 , 46 . As a result, we speculated that lhx4 knockdown via MO in zebrafish is phenotypically similar to human CPHD.…”

Section: Discussionmentioning

confidence: 99%

LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish

Guo

Wang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin+ amacrine cells (ACs) and Rhodopsin+ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.

show abstract

“…All analyses were conducted on DNA extracted from peripheral blood, using the phenol-chloroform method. A highresolution microarray scanning for genomic imbalances was conducted with the use of Affymetrix CytoScanHD arrays (2,7 M, Santa Clara, USA) and GeneChip Scanner 3000 7G (Budny et al 2020a). For an assay, 200 ng of genomic DNA was used.…”

Section: Genetic Testingmentioning

confidence: 99%

CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy

et al. 2021

Self Cite

View full text Add to dashboard Cite

The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study’s aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.

show abstract

Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency

Cited by 10 publications

References 37 publications

Novel genes and variants associated with congenital pituitary hormone deficiency in the era of next-generation sequencing

Novel genes and variants associated with congenital pituitary hormone deficiency in the era of next-generation sequencing

LIM Homeobox 4 (lhx4) regulates retinal neural differentiation and visual function in zebrafish

CDON gene contributes to pituitary stalk interruption syndrome associated with unilateral facial and abducens nerve palsy

Contact Info

Product

Resources

About