Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt

Ziemnicka, Katarzyna; Gut, Paweł; Gołąb, Monika; Dworacki, Grzegorz; Wrotkowska, Elżbieta; Stajgis, Marek; Katulska, Katarzyna; Rabska-Pietrzak, Barbara; Obara-Moszynska, Monika; Niedziela, Marek; Budny, Bartłomiej; Kałużna, Małgorzata; Waśko, Ryszard; Ruchała, Marek

doi:10.1007/s00005-016-0386-x

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…Pituitary Magnetic Resonance Imaging (MRI) was performed in all patients. Methods describing evaluation of hormonal status and pituitary imaging were described in our previous publication (4). In familial cases of the disease, no consanguinity was reported for any of the recruited families.…”

Section: Patientsmentioning

confidence: 99%

SEMA3A and IGSF10 Are Novel Contributors to Combined Pituitary Hormone Deficiency (CPHD)

et al. 2020

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Background: The mutation frequencies of pituitary transcription factors genes in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. However, apart from PROP1 the mutation rate of other genes is low and for almost half of the patients with CPHD the routine sequencing of known genes is unsuccessful in the identification of genetic causes.Methods: A cohort of 66 sporadic and nine familial CPHD cases (80 patients in total) were subjected to initial testing of the genes PROP1, POU1F1, LHX3, LHX4, and HESX1 using a targeted gene panel and MLPA. In patients who tested negative, a whole exome sequencing approach was employed.Results: In nine of the familial cases and 32 of the sporadic patients mutations in the PROP1 gene were found (the common pathogenic variants included c.301_302delAG and c.150delA). Mutations were also found in genes so far not related directly to CPHD. A unique homozygous and clinically relevant variant was identified in the SEMA3A gene, which may contribute to neural development and his phenotypic spectrum including short stature and isolated hypogonadotropic hypogonadism (IHH). Another pathogenic variant p.A1672T was found in the IGSF10 gene reported to be responsible for delayed puberty and neuronal migration during embryogenesis. Several suspected novel but predicted benign variants were also identified for the CHD7, WDR11 and FGF17 genes. Conclusion:Although PROP1 defects account for a majority of CPHD patients, identification of rare, less frequent variants constitutes a big challenge. Multiple genetic factors responsible for CPHD are still awaiting discovery and therefore the usage of efficient genomic tools (i.e., whole exome sequencing) will further broaden our knowledge regarding pituitary development and function.

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Section: Patientsmentioning

confidence: 99%

SEMA3A and IGSF10 Are Novel Contributors to Combined Pituitary Hormone Deficiency (CPHD)

et al. 2020

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“…Moreover, they observed the presence of antibodies against alpha-enolase, gamma-enolase and anti-PGSF1 and anti-PGSF2 (pituitary gland specific factor) in 45% of patients [19]. Ziemnicka et al ., using the immunoblotting method, described pituitary autoantibodies against antigens of weights of 67, 60, 50 and 36 kDa in congenital hypopituitarism patients [20]. Bensing and Kasperlik-Załuska and Czarnocka [21, 22] described the presence of pituitary antibodies in an isolated ACTH deficiency.…”

Section: Discussionmentioning

confidence: 99%

Incidence of pituitary autoantibodies in idiopathic diabetes insipidus

Gut¹,

Czarnywojtek²,

Ziemnicka³

et al. 2018

cejoi

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Diabetes insipidus is a disorder resulting from insufficient action of vasopressin (ADH) characterized by excretion of highly diluted urine in large amounts. Idiopathic diabetes insipidus is associated with the presence of both autoantibodies against ADH-secreting neurons and pituitary autoantibodies. The aim of the present study was to evaluate the occurrence of autoantibodies against the pituitary microsomal fraction. The study included 33 sera of diabetes insipidus patients and 10 control sera obtained from 10 healthy persons. In all patients the secretion of pituitary hormones and thyroid autoantibodies was assessed. Human pituitaries were obtained during autopsy and homogenized in 0.01 mol/l pH 7.4 phosphate buffer. In addition, for the autoantibody evaluation, the electrophoretic method of separation in polyacrylamide gel and western blot were employed. Among the 33 subjects, in 23 patients the presence of autoantibodies against the pituitary was shown. Sera of 15 patients reacted with the pituitary microsomal fraction protein of 55 kDa. In other cases, 10 sera reacted with the pituitary antigen of 67 kDa. In addition, 5 sera reacted with the 60 kDa antigen, 5 sera with 52 kDa protein, 3 sera with 105 kDa protein, 3 sera with the 97 kDa antigen and 2 sera with pituitary antigen of 92 kDa weight. In our study, based on the immunoblotting method, we observed that pituitary autoantibodies against 55, 60 and 67 kDa antigens occurred frequently.

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“…The patient cohort was reported before, in previous publications [16,17]. Briefly, we examined 32 CPHD patients, recruited from the Department of Endocrinology, Metabolism, and Internal Diseases at Poznan University of Medical Sciences.…”

Section: Patientsmentioning

confidence: 99%

Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency

Budny

Karmelita‐Katulska

Stajgis

et al. 2020

IJMS

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Combined pituitary hormone deficiency represents a disorder with complex etiology. For many patients, causes of the disease remain unexplained, despite usage of advanced genetic testing. Although major and common transcription factors were identified two decades ago, we still struggle with identification of rare inborn factors contributing to pituitary function. In this report, we follow up genomic screening of CPHD patient cohort that were previously tested for changes in a coding sequences of genes with the use of the whole exome. We aimed to find contribution of rare copy number variations (CNVs). As a result, we identified genomic imbalances in 7 regions among 12 CPHD patients. Five out of seven regions showed copy gains whereas two presented losses of genomic fragment. Three regions with detected gains encompassed known CPHD genes namely LHX4, HESX1, and OTX2. Among new CPHD loci, the most interesting seem to be the region covering SIX3 gene, that is abundantly expressed in developing brain, and together with HESX1 contributes to pituitary organogenesis as it was evidenced before in functional studies. In conclusion, with the use of broadened genomic approach we identified copy number imbalances for 12 CPHD patients. Although further functional studies are required in order to estimate its true impact on expression pattern during pituitary organogenesis and CPHD etiology.

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Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt

Cited by 4 publications

References 38 publications

SEMA3A and IGSF10 Are Novel Contributors to Combined Pituitary Hormone Deficiency (CPHD)

SEMA3A and IGSF10 Are Novel Contributors to Combined Pituitary Hormone Deficiency (CPHD)

Incidence of pituitary autoantibodies in idiopathic diabetes insipidus

Copy Number Variants Contributing to Combined Pituitary Hormone Deficiency

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