Co-occurrence of an HSPG2 Missense Variant and Functional Polymorphisms in Atypical Schwartz–Jampel Syndrome Type 1 with Obesity: A Case Report

2018 ◽  
Vol 17 (04) ◽  
pp. 149-152
Author(s):  
Ilenia Maini ◽  
Enrico Farnetti ◽  
Davide Nicoli ◽  
Elena Pavlidis ◽  
Carlotta Spagnoli ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Phenotypic Variability ◽  
Clinical Signs ◽  
Missense Variant ◽  
Syndrome Type ◽  
Sulfate Proteoglycan ◽  
Functional Polymorphisms ◽  
Clinical Exome Sequencing ◽  
Genetic Result

AbstractSchwartz–Jampel syndrome type 1 (SJS1) is an autosomal recessive chondrodystrophic myotonia, linked to heparan sulfate proteoglycan 2 (HSPG2) variants. We describe a patient with typical features of SJS1, but not obesity. Clinical exome sequencing detected a rare missense variant in HSPG2, confirming our clinical diagnosis, but also two homozygous variants in SDC3 and ADRB3 genes, previously described to be associated with obesity. This additional genetic result could better explain our patient's phenotype. Despite the phenotypic variability associated to HSPG2 variants, it is advisable to carefully check other possible genetic causes underlying clinical signs not strictly related to the classical phenotype of SJS1.

scholarly journals Distribution of the Warmblood Fragile Foal Syndrome Type 1 Mutation (PLOD1 c.2032G>A) in Different Horse Breeds from Europe and the United States

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1518
Author(s):  
Simone Reiter ◽  
Barbara Wallner ◽  
Gottfried Brem ◽  
Elisabeth Haring ◽  
Ludwig Hoelzle ◽  
...  
Keyword(s):  
United States ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
The United States ◽  
Syndrome Type ◽  
Reference Allele ◽  
Single Nucleotide ◽  
Similar Phenotype ◽  
The 19Th Century

Warmblood fragile foal syndrome (WFFS) is an autosomal recessive disorder caused by a single nucleotide variant in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg). Homozygosity for the PLOD1 variant causes an Ehler-Danlos-like syndrome, which has to date only been reported in warmblood breeds but the WFFS allele has been also detected in the Thoroughbred. To investigate the breed distribution of the WFFS allele, 4081 horses belonging to 38 different breeds were screened. In total, 4.9% of the horses representing 21 breeds carried the WFFS allele. The affected breeds were mainly warmbloods, with carrier frequency as high as 17% in the Hanoverian and Danish Warmblood. The WFFS allele was not detected in most non-warmblood breeds. Exceptions include WFFS carriers in the Thoroughbred (17/716), Haflinger (2/48), American Sport Pony (1/12), and Knabstrupper (3/46). The origin of the WFFS allele remains unknown. The Arabian breed and specifically the stallion Bairactar Or. Ar. (1813), whose offspring were reported to have a similar phenotype in the 19th century, were hypothesized as the origin. DNA from a museum sample of Bairactar Or. Ar. showed that he did not carry the mutated allele. This result, together with the genotypes of 302 Arabians, all homozygous for the reference allele, does not support an Arabian origin of the WFFS allele. Our extensive survey shows the WFFS allele to be of moderate frequency and concern in warmbloods and also in breeds where it may not be expected.

scholarly journals Bartter Syndrome Type 1 Presenting as Nephrogenic Diabetes Insipidus

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Gianluca Vergine ◽  
Elena Fabbri ◽  
Annalisa Pedini ◽  
Silvana Tedeschi ◽  
Niccolò Borsa
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Metabolic Alkalosis ◽  
Phenotypic Variability ◽  
Bartter Syndrome ◽  
Syndrome Type ◽  
Renal Tubular Disorder ◽  
Renal Tubular ◽  
Genetically Determined

Bartter syndrome (BS) type 1 (OMIM #601678) is a hereditary salt-losing renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypercalciuria, nephrocalcinosis, polyuria, recurrent vomiting, and growth retardation. It is caused by loss-of-function mutations of the SLC12A1 gene, encoding the furosemide-sensitive Na-K-Cl cotransporter. Recently, a phenotypic variability has been observed in patients with genetically determined BS, including absence of nephrocalcinosis, hypokalemia, and/or metabolic alkalosis in the first year of life as well as persistent metabolic acidosis mimicking distal renal tubular acidosis. We report the case of a child with a genetically determined diagnosis of Bartter syndrome type 1 who presented with a phenotype of nephrogenic diabetes insipidus, with severe hypernatremia and urinary concentrating defect. In these atypical cases, molecular analysis is mandatory to define the diagnosis, in order to establish the correct clinical and therapeutic management.

scholarly journals Autosomal recessive long QT syndrome, type 1 in eight families from Saudi Arabia

2017 ◽  
Vol 5 (5) ◽  
pp. 592-601 ◽  
Author(s):  
Amnah Y. Bdier ◽  
Saleh Al-Ghamdi ◽  
Prashant K. Verma ◽  
Khalid Dagriri ◽  
Bandar Alshehri ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Long Qt Syndrome ◽  
Autosomal Recessive ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome

KCNQ1mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India-expanding the spectrum of long QT syndrome type 1

2016 ◽  
Vol 170 (6) ◽  
pp. 1510-1519 ◽  
Author(s):  
Bijal Vyas ◽  
Ratna D. Puri ◽  
Narayanan Namboodiri ◽  
Mohan Nair ◽  
Deepak Sharma ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Autosomal Recessive ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome

scholarly journals The recurrent missense mutation p.(Arg367Trp) in YARS1 causes a distinct neurodevelopmental phenotype

2021 ◽  
Author(s):  
Luisa Averdunk ◽  
Heinrich Sticht ◽  
Harald Surowy ◽  
Hermann-Josef Lüdecke ◽  
Margarete Koch-Hogrebe ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Catalytic Domain ◽  
Clinical Signs ◽  
Missense Variant ◽  
Protein Translation ◽  
Trna Synthetase ◽  
Functional Domains ◽  
List Type ◽  
Multisystem Disorder ◽  
Pathogenic Variants

Abstract Pathogenic variants in aminoacyl-tRNA synthetases (ARS1) cause a diverse spectrum of autosomal recessive disorders. Tyrosyl tRNA synthetase (TyrRS) is encoded by YARS1 (cytosolic, OMIM*603,623) and is responsible of coupling tyrosine to its specific tRNA. Next to the enzymatic domain, TyrRS has two additional functional domains (N-Terminal TyrRSMini and C-terminal EMAP-II-like domain) which confer cytokine-like functions. Mutations in YARS1 have been associated with autosomal-dominant Charcot-Marie-Tooth (CMT) neuropathy type C and a heterogenous group of autosomal recessive, multisystem diseases. We identified 12 individuals from 6 families with the recurrent homozygous missense variant c.1099C > T;p.(Arg367Trp) (NM_003680.3) in YARS1. This variant causes a multisystem disorder with developmental delay, microcephaly, failure to thrive, short stature, muscular hypotonia, ataxia, brain anomalies, microcytic anemia, hepatomegaly, and hypothyroidism. In silico analyses show that the p.(Arg367Trp) does not affect the catalytic domain responsible of enzymatic coupling, but destabilizes the cytokine-like C-terminal domain. The phenotype associated with p.(Arg367Trp) is distinct from the other biallelic pathogenic variants that reside in different functional domains of TyrRS which all show some common, but also divergent clinical signs [(e.g., p.(Phe269Ser)—retinal anomalies, p.(Pro213Leu)/p.(Gly525Arg)—mild ID, p.(Pro167Thr)—high fatality)]. The diverse clinical spectrum of ARS1-associated disorders is related to mutations affecting the various non-canonical domains of ARS1, and impaired protein translation is likely not the exclusive disease-causing mechanism of YARS1- and ARS1-associated neurodevelopmental disorders. Key messages The missense variant p.(Arg367Trp) in YARS1 causes a distinct multisystem disorder. p.(Arg367Trp) affects a non-canonical domain with cytokine-like functions. Phenotypic heterogeneity associates with the different affected YARS1 domains. Impaired protein translation is likely not the exclusive mechanism of ARS1-associated disorders.

scholarly journals Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region

2021 ◽  
Author(s):  
Peter J Schwartz ◽  
Cristina Moreno ◽  
Maria-Christina Kotta ◽  
Matteo Pedrazzini ◽  
Lia Crotti ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Cyclic Adenosine Monophosphate ◽  
Missense Variant ◽  
Adenosine Monophosphate ◽  
Dominant Negative ◽  
Clinical Severity ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome

Abstract Aims Mutation type, location, dominant-negative IKs reduction, and possibly loss of cyclic adenosine monophosphate (cAMP)-dependent IKs stimulation via protein kinase A (PKA) influence the clinical severity of long QT syndrome type 1 (LQT1). Given the malignancy of KCNQ1-p.A341V, we assessed whether mutations neighbouring p.A341V in the S6 channel segment could also increase arrhythmic risk. Methods and results Clinical and genetic data were obtained from 1316 LQT1 patients [450 families, 166 unique KCNQ1 mutations, including 277 p.A341V-positive subjects, 139 patients with p.A341-neighbouring mutations (91 missense, 48 non-missense), and 900 other LQT1 subjects]. A first cardiac event represented the primary endpoint. S6 segment missense variant characteristics, particularly cAMP stimulation responses, were analysed by cellular electrophysiology. p.A341-neighbouring mutation carriers had a QTc shorter than p.A341V carriers (477 ± 33 vs. 490 ± 44 ms) but longer than the remaining LQT1 patient population (467 ± 41 ms) (P < 0.05 for both). Similarly, the frequency of symptomatic subjects in the p.A341-neighbouring subgroup was intermediate between the other two groups (43% vs. 73% vs. 20%; P < 0.001). These differences in clinical severity can be explained, for p.A341V vs. p.A341-neighbouring mutations, by the p.A341V-specific impairment of IKs regulation. The differences between the p.A341-neighbouring subgroup and the rest of LQT1 mutations may be explained by the functional importance of the S6 segment for channel activation. Conclusion KCNQ1 S6 segment mutations surrounding p.A341 increase arrhythmic risk. p.A341V-specific loss of PKA-dependent IKs enhancement correlates with its phenotypic severity. Cellular studies providing further insights into IKs-channel regulation and knowledge of structure-function relationships could improve risk stratification. These findings impact on clinical management.

scholarly journals Autoimmune polyendocrine syndrome type 1: case report and review of literature

2012 ◽  
Vol 56 (1) ◽  
pp. 54-66 ◽  
Author(s):  
Fernanda Guimarães Weiler ◽  
Magnus R. Dias-da-Silva ◽  
Marise Lazaretti-Castro
Keyword(s):  
Autosomal Recessive ◽  
Clinical Course ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Syndrome Type ◽  
Adrenal Failure ◽  
Review Of Literature ◽  
Autoimmune Polyendocrine Syndrome

Autoimmune polyendocrine syndrome type 1 (APECED) is a rare autosomal recessive disorder characterized by autoimmune multiorgan attack. The disease is caused by mutations in the autoimmune regulator gene (AIRE), resulting in defective AIRE protein, which is essential for selftolerance. Clinical manifestations are widely variable. Although the classic triad is composed by mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, many other components may develop. Treatment is based on supplementation of the various deficiencies, and patients require regular follow-up throughout their lifespan. This article describes the case of a patient with the disease, and reviews literature data on the epidemiology, clinical course, immunogenetic aspects, diagnosis and treatment of the syndrome.

scholarly journals Intramuscular neridronate for the treatment of complex regional pain syndrome type 1: a randomized, double-blind, placebo-controlled study

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110140
Author(s):  
Massimo Varenna ◽  
Vania Braga ◽  
Davide Gatti ◽  
Giovanni Iolascon ◽  
Bruno Frediani ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Pain Syndrome ◽  
Signs And Symptoms ◽  
Mcgill Pain Questionnaire ◽  
Syndrome Type ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Sf 36 ◽  
Clinical Signs And Symptoms

Background: Complex regional pain syndrome type-1 (CRPS-1) is a severely disabling painful disease challenging to treat. This multicenter, randomized, double-blind placebo-controlled trial examined the efficacy of intramuscular (i.m.) neridronate in CRPS-1 patients. Methods: A total of 78 patients diagnosed with CRPS-1 (aged 59.5 ± 10.3, 66.7% female) were randomly assigned to 25 mg (i.m.) neridronate ( N = 41) given once daily for 16 consecutive days or placebo control ( N = 37). Efficacy was assessed after 30 days using a visual analogue scale (VAS) pain score and the number of patients achieving ⩾50% reduction in VAS score. Change in clinical signs and symptoms, quality of life (QoL) using Short Form Health Survey (SF-36) and the McGill Pain Questionnaire were also assessed. Results: After 30 days, VAS score decreased significantly to a greater extent in neridronate-treated patients versus placebo (31.9 ± 23.3 mm versus 52.3 ± 27.8 mm, p = 0.0003). Furthermore, the proportion of patients achieving a VAS reduction of ⩾50% was greater in the neridronate group (65.9% versus 29.7%, p = 0.0017). Clinical signs and symptoms were improved significantly in the neridronate group versus placebo for edema (72.5% versus 79.9%, p = 0.03), pain during motion (70% versus 83.3%, p = 0.0009), allodynia (20% versus 63.3%, p = 0.0004), and hyperalgesia (20% versus 56.7%, p = 0.0023). Whereas no difference was observed for QoL measures using the SF-36 questionnaire, three of the four pain variables using the McGill Pain Questionnaire improved significantly in the neridronate group. No serious drug-related adverse events were reported during the study. Conclusion: In patients with acute CRPS-1, i.m. injections of 25 mg neridronate were associated with clinically relevant benefit compared with placebo controls. Trial registration: EU Clinical Trials Register: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001156-28

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