A Novel Missense Mutation in Human Receptor Roundabout-1 &lt;i&gt;(ROBO1)&lt;/i&gt; Gene Associated with Pituitary Stalk Interruption Syndrome

Liu, Ziqin; Chen, Xiaobo

doi:10.4274/jcrpe.galenos.2019.2018.0309

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…Malfunctioning of ROBO1 due to missense mutations has been associated with neurological disorders in humans [30]. Since our report in 2014, several studies have emerged focused on the role of ROBO1 in human cancers [9,31].…”

Section: Author Manuscriptmentioning

confidence: 99%

Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

et al. 2020

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Background: There is a need to develop novel therapies which could be beneficial to prostate cancer (CaP) patients including those who are predisposed to poor outcome such as African-Americans. This study investigates the role of ROBO1-pathway in predicting outcome and race-based disparity in CaP patients. Methods and Results:Aided by RNA sequencing-based DECIPHER-testing and IHC analysis of tumors we show that ROBO1 is lost during the progressive stages of CaP, a prevalent feature in African-Americans. We show that the loss of ROBO1 predicts high-risk of recurrence, metastasis and poor outcome of ADT

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Section: Author Manuscriptmentioning

confidence: 99%

Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

et al. 2020

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“…To add further complexity to the interpretation of the data, the child also carries a rare missense variant in ROBO1 . ROBO1 variants are associated with PSIS and optic nerve anomalies [ 17 , 26 , 27 ]. It is possible that the complex phenotype may be due to contributions of each of these variants.…”

Section: Resultsmentioning

confidence: 99%

“…nerve anomalies [17,26,27]. It is possible that the complex phenotype may be due to contributions of each of these variants.…”

Section: Plos Onementioning

confidence: 99%

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

2020

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Pituitary stalk interruption syndrome is a rare disorder characterized by an absent or ectopic posterior pituitary, interrupted pituitary stalk and anterior pituitary hypoplasia, as well as in some cases, a range of heterogeneous somatic anomalies. A genetic cause is identified in only around 5% of all cases. Here, we define the genetic variants associated with PSIS followed by the same pediatric endocrinologist. Exome sequencing was performed in 52 (33 boys and 19 girls), including 2 familial cases single center pediatric cases, among them associated 36 (69.2%) had associated symptoms or syndromes. We identified rare and novel variants in genes (37 families with 39 individuals) known to be involved in one or more of the following—midline development and/or pituitary development or function (BMP4, CDON, GLI2, GLI3, HESX1, KIAA0556, LHX9, NKX2-1, PROP1, PTCH1, SHH, TBX19, TGIF1), syndromic and non-syndromic forms of hypogonadotropic hypogonadism (CCDC141, CHD7, FANCA, FANCC, FANCD2, FANCE, FANCG, IL17RD, KISS1R, NSMF, PMM2, SEMA3E, WDR11), syndromic forms of short stature (FGFR3, NBAS, PRMT7, RAF1, SLX4, SMARCA2, SOX11), cerebellum atrophy with optic anomalies (DNMT1, NBAS), axonal migration (ROBO1, SLIT2), and agenesis of the corpus callosum (ARID1B, CC2D2A, CEP120, CSPP1, DHCR7, INPP5E, VPS13B, ZNF423). Pituitary stalk interruption syndrome is characterized by a complex genetic heterogeneity, that reflects a complex phenotypic heterogeneity. Seizures, intellectual disability, micropenis or cryptorchidism, seen at presentation are usually considered as secondary to the pituitary deficiencies. However, this study shows that they are due to specific gene mutations. PSIS should therefore be considered as part of the phenotypic spectrum of other known genetic syndromes rather than as specific clinical entity.

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“…The etiology of PSIS is not known. The proposed pathophysiological mechanism of PSIS is mutation in the genes (PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF, HESX1, [ 7 ] ROBO1, [ 8 ] and GPR161 [ 9 ] ) involved in the development of the anterior pituitary. Undescended testes and micropenis might be associated with genetic mutations in the HESX1, LHX4, and SOX3 genes.…”

Section: Discussionmentioning

confidence: 99%

Pituitary stalk interruption syndrome

Zhang¹,

Qian²,

Guan³

et al. 2020

Medicine

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Rationale: Pituitary stalk interruption syndrome (PSIS) is a congenital pituitary anatomical defect. It is characterized by the triad of thin or interrupted pituitary stalk, absent or ectopic posterior lobe, and hypoplastic or aplastic anterior lobe. Moreover, this condition is considered rare. Patient concerns: A 23-year-old male patient presented with a history of short stature and hypogonadism. Laboratory assessment revealed low thyroxine, cortisol, and adrenocorticotropic hormone levels, which are consistent with adrenal insufficiency without hypoglycemia. The insulin-induced hypoglycemia tolerance test finding indicated growth hormone (GH) deficiency. Moreover, magnetic resonance imaging revealed an interrupted pituitary stalk, ectopic posterior pituitary, and hypoplastic anterior pituitary. This triad of symptoms was indicative of PSIS. Diagnosis: PSIS; hypopituitarism: secondary hypothyroidism, secondary adrenocortical dysfunction, hypogonadotropic hypogonadism, and GH deficiency; sphenoid sinus cyst; osteoporosis; hyperinsulinism; and dyslipidemia. Interventions: The patient was deficient in adrenaline, thyroxine, gonadal steroid, and GH. Thus, glucocorticoid replacement therapy was initiated, followed by euthyrox, androgen, and human chorionic gonadotropin treatment. Calcium tablets, calcitriol, and alendronate sodium were used for the management of osteoporosis. The patient was 164 cm tall, and his bone age was approximately 15 years old. However, owing to a poor economic condition, the family did not proceed with GH therapy. Outcomes: The patient did not present with adrenal or hypothyroidism crisis after receiving poly-hormonal replacement therapy. His secondary sexual characteristics began to develop. However, owing to a short treatment window period, the patient could not receive the required treatment. Hence, whether the patient would have a normal fertility function needs to be confirmed. Lessons: PSIS is a rare disease with various clinical characteristics. During the neonatal period and infancy, the signs and symptoms of PSIS are often not evident. Therefore, diagnosis is delayed. The early detection of hormone deficiency and treatment initiation can affect both the quality of life and the prognosis of patients with PSIS. Thus, the diagnosis and treatment of this disease must be improved to help patients achieve a better quality of life and to prevent reproductive health problems.

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A Novel Missense Mutation in Human Receptor Roundabout-1 <i>(ROBO1)</i> Gene Associated with Pituitary Stalk Interruption Syndrome

Cited by 14 publications

References 23 publications

Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

Pituitary stalk interruption syndrome

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A Novel Missense Mutation in Human Receptor Roundabout-1 <i>(ROBO1)</i> Gene Associated with Pituitary Stalk Interruption Syndrome

Cited by 14 publications

References 23 publications

Identifying and treating ROBO1−ve/DOCK1+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

Identifying and treating ROBO1−ve/DOCK1+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

Pituitary stalk interruption syndrome

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Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients

Identifying and treating ROBO1^−ve/DOCK1^+ve prostate cancer: An aggressive cancer subtype prevalent in African American patients