15q Duplication Syndrome: Report on the First Patient from Ecuador with an Unusual Clinical Presentation

Background. The 15q11.1-13.1 duplication, also known as Dup15q syndrome, is a rare congenital disease affecting 1 in 30,000 to 1 in 60,000 children worldwide. This condition is characterized by the presence of at least one extra copy of genetical material within the Prader-Willi/Angelman Critical Region (PWACR) of the referred 15q11.2-q13.1 chromosome. Case Report. Our study presents the clinical and genetical features of the first patient with a denovo 15q11.2 interstitial duplication on the maternal allele (inv Dup15q) that mimics a milder Prader-Willi syndrome probably due to an atypical disruption of the SNHG14 gene. Methylation-specific MLPA analysis has confirmed the presence of a very unlikely duplication that lies between breakpoint 1 (BP1) and the middle of BP2 and BP3 (BP3). This atypical alteration might be linked to the milder patient’s clinical phenotype. Conclusions. This is the first Dup15q patient reported in Ecuador and of the very few in South America. This aberration has never been described in a patient with Dup15q, and the unusual clinical presentation is probably due to the atypical distal breakpoint occurring within the gene SNHG14 which lies between BP2 and BP3 and does not therefore contain the whole PWACR. If the duplication disrupted the gene, then it is possible that it is the cause of, or contributing to, the patient’s clinical phenotype.

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Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

Current Medicinal Chemistry ◽

10.2174/0929867327666200730214757 ◽

2020 ◽

Vol 27 ◽

Author(s):

Daniela Fanni ◽

Clara Gerosa ◽

Valeria Marina Nurchi ◽

Rosita Cappai ◽

Marta Mureddu ◽

...

Keyword(s):

Wilson Disease ◽

Clinical Presentation ◽

Clinical Phenotype ◽

Methylation Status ◽

Copper Metabolism ◽

Epigenetic Factors ◽

Genetic Changes ◽

Illness Onset ◽

Phenotypic Manifestation ◽

Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

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Electro-clinical features in epileptic children with chromosome 15q duplication syndrome

Clinical Neurophysiology ◽

10.1016/j.clinph.2021.02.010 ◽

2021 ◽

Vol 132 (5) ◽

pp. 1126-1137

Author(s):

M.-T. Dangles ◽

V. Malan ◽

G. Dumas ◽

S. Romana ◽

O. Raoul ◽

...

Keyword(s):

Clinical Features ◽

15Q Duplication ◽

Epileptic Children ◽

Duplication Syndrome

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Letter to the Editor

PEDIATRICS ◽

10.1542/peds.43.5.905b ◽

1969 ◽

Vol 43 (5) ◽

pp. 905-906

Author(s):

Aubrey Milunsky

Keyword(s):

Cystic Fibrosis ◽

Bone Marrow ◽

Clinical Presentation ◽

Pancreatic Insufficiency ◽

Chloride Concentration ◽

Letter To The Editor ◽

Patient Reported ◽

Sweat Sample ◽

Chloride Concentrations

The patient reported in the foregoing letter is of particular interest in view of the recent observations on patients with tnisomy 21 and cystic fibrosis. The multiple possibilities that could explain the clinical presentation have no doubt been considered by the authors. However, the description of "hypoplastic thrombocytopenia" and later pancytopenia in this patient, associated with pancreatic insufficiency, leads to the serious consideration of Shwachman's syndrome (pancreatic insufficiency and bone marrow dysfunction). The wide discrepancy between the sodium and chloride concentrations in the sweat reported in their letter indicates that evaporation of water may have occurred from the sweat sample, leading to an apparently higher sodium and chloride concentration.

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Functional neuroplasticity in response to cerebello-thalamic injury underpins the clinical presentation of tremor in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458519837706 ◽

2019 ◽

Vol 26 (6) ◽

pp. 696-705 ◽

Cited By ~ 3

Author(s):

Frederique MC Boonstra ◽

Gustavo Noffs ◽

Thushara Perera ◽

Vilija G Jokubaitis ◽

Adam P Vogel ◽

...

Keyword(s):

Multiple Sclerosis ◽

Supplementary Motor Area ◽

Clinical Presentation ◽

Clinical Phenotype ◽

Premotor Cortex ◽

Brain Structures ◽

Lesion Load ◽

Spiral Drawing ◽

Brain Changes ◽

Functional Neuroplasticity

Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments. Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS. Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0–10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified. Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor ( p < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity. Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

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Characteristics and Clinical Outcomes of Open Surgery for Trigger Digits in Diabetes

Journal of Hand and Microsurgery ◽

10.1055/s-0038-1670927 ◽

2018 ◽

Vol 11 (02) ◽

pp. 080-083

Author(s):

Sean Wei Loong Ho ◽

Ching Yee Chia ◽

Vaikunthan Rajaratnam

Keyword(s):

Clinical Outcomes ◽

Open Surgery ◽

Clinical Presentation ◽

Clinical Severity ◽

High Rate ◽

Dominant Hand ◽

Diabetes Group ◽

Initial Surgery ◽

Patient Reported ◽

Surgical Release

Abstract Introduction Trigger digit is a common condition of the hand. Diabetes has a known association with the development of trigger digit. It is thought to influence the clinical presentation and efficacy of open surgical release. This study aimed to assess the differential characteristics of trigger digits and the clinical outcomes of open surgery for trigger digits in diabetics. Materials and Methods This was a retrospective study of all patients who underwent open surgical release of trigger digits in a single institution from 2012 to 2013. Patients were divided into two groups with group 1 consisting of all patients with a history of diabetes. Group 2 consisted of all patients without diabetes. Demographics and clinical presentation were reviewed. All patients were reviewed via a telephone questionnaire at least 2 years after the initial surgery and were assessed for patient-reported outcomes. Results There were 201 patients who met the inclusion criteria, of which 191 patients were recruited. This included 87 (45.5%) males and 104 (54.5%) females. A total of 260 open releases were performed. Sixty-one (31.9%) patients were diabetic, and 130 (68.1%) patients were nondiabetic. The diabetic group was significantly older than the nondiabetic group (p = 0.002). The dominant hand was not significantly more affected than the nondominant hand (p = 0.51). The middle finger was most commonly involved (43.5%), and the little finger was the least commonly involved (1.2%). There was no significant increase in multiple-digit presentation in the diabetic population when compared with the nondiabetic population (p = 0.52). There was a low complication rate and a high rate of postoperative satisfaction after open surgery in both groups. Conclusion Diabetes does not predispose patients to increased rates of multiple trigger digit presentation or increased clinical severity on presentation. Open surgery for trigger digit is an effective and safe treatment modality for diabetics.

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A survey of seizures and current treatments in 15q duplication syndrome

Epilepsia ◽

10.1111/epi.12530 ◽

2014 ◽

Vol 55 (3) ◽

pp. 396-402 ◽

Cited By ~ 53

Author(s):

Kerry D. Conant ◽

Brenda Finucane ◽

Nicole Cleary ◽

Ashley Martin ◽

Candace Muss ◽

...

Keyword(s):

15Q Duplication ◽

Duplication Syndrome

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Transcriptome profiling of white adipose tissue in a mouse model for 15q duplication syndrome

Genomics Data ◽

10.1016/j.gdata.2015.06.035 ◽

2015 ◽

Vol 5 ◽

pp. 394-396 ◽

Cited By ~ 3

Author(s):

Xiaoxi Liu ◽

Kota Tamada ◽

Rui Kishimoto ◽

Hiroko Okubo ◽

Satoko Ise ◽

...

Keyword(s):

Adipose Tissue ◽

Mouse Model ◽

White Adipose Tissue ◽

Transcriptome Profiling ◽

15Q Duplication ◽

Duplication Syndrome

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Gastrointestinal problems in 15q duplication syndrome

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2014.12.012 ◽

2015 ◽

Vol 58 (3) ◽

pp. 191-193 ◽

Cited By ~ 6

Author(s):

Elias A. Shaaya ◽

Sarah F. Pollack ◽

Susana Boronat ◽

Shelby Davis-Cooper ◽

Garrett C. Zella ◽

...

Keyword(s):

15Q Duplication ◽

Gastrointestinal Problems ◽

Duplication Syndrome

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Case Report: Corneal Leucoma as a Novel Clinical Presentation of Nail-Patella Syndrome in a 5-Year-Old Girl

Frontiers in Pediatrics ◽

10.3389/fped.2021.638630 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ling Hou ◽

Yue Du ◽

Yubin Wu ◽

Yue Zeng ◽

Chengguang Zhao

Keyword(s):

Nephrotic Syndrome ◽

Clinical Presentation ◽

De Novo ◽

Autosomal Dominant Disorder ◽

Steroid Resistant ◽

Steroid Resistant Nephrotic Syndrome ◽

Psychomotor Delay ◽

Bilateral Absence ◽

Patient Reported ◽

Nail Patella Syndrome

Nail-patella syndrome (NPS) is a rare autosomal-dominant disorder characterized by the classic tetrad of absent or hypoplastic finger and toe nails, absent or hypoplastic patella, skeletal deformities involving the elbow joints, and iliac horns. This disease is caused by heterozygous pathogenic variations in the LMX1B gene, which encodes the LIM homeodomain transcription factor protein (LMX1B). We report a case of corneal leucoma and dysplasia prior to overt steroid-resistant nephrotic syndrome (SRNS) in a patient with NPS. At presentation, the parents of a 5-year-old female patient reported their daughter had corneal leucoma, psychomotor delay and speech defect. We also noted the presence of bilateral edema of the lower extremities, hypertension, nail dystrophy, and the bilateral absence of patella. She developed steroid-resistant nephrotic syndrome. Lowe oculocerebrorenal syndrome and NPS were the conditions considered in differential diagnosis. Trio-based whole genome sequencing indicated a heterozygous de novo likely pathogenic variation in the LMX1B gene (c.805A>C [p.Asn269His]). Patients with NPS often develop nail, ocular, or orthopedic symptoms prior to nephrotic syndrome. Corneal leucoma may be a novel clinical presentation of NPS.

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The Importance of Classical and Molecular Cytogenetics in the Diagnosis of Microdeletions Microduplications Syndromes

Revista de Chimie ◽

10.37358/rc.20.5.8147 ◽

2020 ◽

Vol 71 (5) ◽

pp. 373-379

Author(s):

Cristina Annemarie Popa ◽

Maria Puiu ◽

Nicoleta Ioana Andreescu ◽

Daniel Popa ◽

George Puenea ◽

...

Keyword(s):

Trisomy 21 ◽

Digeorge Syndrome ◽

Chromosomal Abnormalities ◽

Genetic Material ◽

Deletion Syndrome ◽

15Q Duplication ◽

Cytogenetic Technique ◽

Duplication Syndrome ◽

Double Aneuploidy

Microdeletions and microduplications syndromes are a well defined group of disorders characterized by loss/ addition of less than 5 Mb of genetic material undetectable by simple karyotype and a particular phenotype. Our study presents the results of investigations of classical and molecular cytogenetic (FISH, Fluorescence in situ Hibridization) in 70 children showing different phenotypic manifestations, such as multiple congenital anomalies, dysmorphic appearance, mental retardation, obesity. After performing classical cytogenetic technique of the 70 cases, in four girls there were diagnosed two visible structural chromosomal abnormalities: DiGeorge syndrome, Distal 18q Deletion syndrome, 15q Duplication syndrome, izocromosome Xq and one boy with 11q24-qter deletion and 38 numerical aberrations were identified: 33 cases of trisomy 21, two cases of monosomy X, two cases of poly Y syndrome and one double aneuploidy, trisomy 21 and poly Y. Using FISH (Fluorescence in situ Hibridization) technique in all the 32 cases, another 5 cases were diagnosed with Prader-Willi syndrome, one with the following: Angelman syndrome, Williams syndrome and 15q Duplication Syndrome, two DiGeorge syndrome, one Jacobsen syndrome, 11q 23-qter deletion and one double aneuploidy. In our study, the efficacy of the classical cytogenetic technique in confirmation of the cases suspected by chromosome abnormality was 61.4% and the FISH technique, was 37,5%.In our study, using both methods of diagnosis, we obtained confirmation of the genetic etiology in only 72.85% of the cases.

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