Novel Genetic Diagnoses in Septo-Optic Dysplasia

Reis, Linda M.; Seese, Sarah E; Maheshwari, Mohit; Basel, Donald; Weik, LuAnn; McCarrier, Julie; Semina, Elena V.

doi:10.3390/genes13071165

Cited by 5 publications

(4 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phenotypic variability, including variable penetrance, is commonly observed in human midline disorders and is characteristic of multifactorial syndromes like HPE, SOD, and CH [109][110][111]. The phenotypic variability observed in both mice and humans highlights the role that chance, stochastic factors, genetic modifiers, and environmental exposures have in determining phenotype [112]. Many of the candidate genes identified here are associated with severe malformations in other tissues.…”

Section: Discussionmentioning

confidence: 77%

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

Martinez-Mayer,

Brinkmeier,

O’Connell

et al. 2024

Genome Med

View full text Add to dashboard Cite

Background Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). Methods The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. Results Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. Conclusions The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.

show abstract

Section: Discussionmentioning

confidence: 77%

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

Martinez-Mayer,

Brinkmeier,

O’Connell

et al. 2024

Genome Med

View full text Add to dashboard Cite

show abstract

“…Thus, SOD patients can suffer from isolated GH deficiency (GHD), CPHD and/or diabetes insipidus. Whereas the most common disease-causing mutations are found in HESX1 , SOX2 and other genes, recently a causative variant in SHH in a SOD family has been identified ( 74 ). Mice with a conditional Shh deletion in the hypothalamus recapitulate this SOD phenotype (see above) ( 10 ).…”

Section: Hh Signaling In the Diseased Pituitarymentioning

confidence: 99%

“…ARNT2, BMP4, FGF8, FGFR1, HESX1, KAL1, OTX2, PAX6, PROKR2, SOX2, SOX3, SHH, (GLI2) (71-73) … inactivation due to SHH, (GLI2) germline mutations(74) …”

mentioning

confidence: 99%

The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis

2023

View full text Add to dashboard Cite

Hedgehog signaling plays pivotal roles in embryonic development, adult homeostasis and tumorigenesis. However, its engagement in the pituitary gland has been long underestimated although Hedgehog signaling and pituitary embryogenic development are closely linked. Thus, deregulation of this signaling pathway during pituitary development results in malformation of the gland. Research of the last years further implicates a regulatory role of Hedgehog signaling in the function of the adult pituitary, because its activity is also interlinked with homeostasis, hormone production, and most likely also formation of neoplasms of the gland. The fact that this pathway can be efficiently targeted by validated therapeutic strategies makes it a promising candidate for treating pituitary diseases. We here summarize the current knowledge about the importance of Hedgehog signaling during pituitary development and review recent data that highlight the impact of Hedgehog signaling in the healthy and the diseased adult pituitary gland.

show abstract

“…transcripción involucrados en la DSO, como HESX1, SOX3, SOX2 y OTX2 [21][22][23] . Más recientemente, la detección de variantes patogénicas en SHH y ARID1A expande el espectro fenotípico asociado a estos genes 24 .…”

Section: B Aunclassified

Resultado a largo plazo de una serie de fetos con agenesia aislada del septum pellucidum

Viñals,

Hormazábal,

Viñals

et al. 2023

RECHOG

View full text Add to dashboard Cite

Objetivo: Reportar el resultado a largo plazo de una serie de fetos con agenesia del septum pellucidum aislada (ASP), con medición de su quiasma óptico mediante neurosonografía fetal (NSG). Método: Se incluyeron todas las pacientes con ASP y NSG evaluadas desde el año 2008 a la fecha y con seguimiento hasta su edad escolar. En todos los casos se consignaron los datos clínicos de NSG y de resonancia magnética (RM), cuando esta se realizó. Se entrevistó telefónicamente a los padres. Resultados: Nueve pacientes cumplieron los criterios: cuatro con displasia septo-óptica (DSO) (rango de seguimiento: 5-14 años) y cinco sin DSO (rango de seguimiento: 7-10 años). Un décimo caso se excluyó por tener solo 6 meses de seguimiento. Ninguna de las ASP tuvo otra anomalía detectada en su seguimiento. Ninguno de los casos con DSO tuvo alteración del tamaño de su quiasma óptico en la NSG ni anormalidad en la vía óptica en la RM. Conclusiones: En nuestra población, el riesgo residual de DSO frente a ASP es del 44,4%. En el seguimiento, nuestra definición de ASP por NSG no tuvo falsos negativos con relación a otras anomalías de aparición posnatal, a excepción de la DSO.

show abstract

Novel Genetic Diagnoses in Septo-Optic Dysplasia

Cited by 5 publications

References 33 publications

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis

Resultado a largo plazo de una serie de fetos con agenesia aislada del septum pellucidum

Contact Info

Product

Resources

About