Johanson–Blizzard's Syndrome with a Novel UBR1 Mutation

2020 ◽  
Author(s):  
Damla Demir ◽  
Yasemin Kendir Demirkol ◽  
Nelgin Gerenli ◽  
Ezgi Aktaş Karabay
Keyword(s):  
Autosomal Recessive ◽  
Frameshift Mutation ◽  
Genetic Disorder ◽  
Pancreatic Insufficiency ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Exocrine Pancreatic Insufficiency ◽  
Ubiquitin Protein Ligase ◽  
Scalp Defect ◽  
Facial Dysmorphia

AbstractJohanson–Blizzard syndrome (JBS) is a rare autosomal recessive genetic disorder, characterized by exocrine pancreatic insufficiency, a distinct abnormal facial appearance and varying degrees of growth retardation. Ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene mutations are responsible for the syndrome. Here, we describe a 2-month-old female infant, who presented with oily diarrhea, facial dysmorphia, scalp defect, hearing defects, and growth impairment. Molecular genetic testing revealed a novel frameshift mutation in UBR1, c.4027_4028 del (p.Leu1343Valfs*7), which was not previously described in JBS in the literature.

scholarly journals The Shwachman-Diamond SBDS protein localizes to the nucleolus

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1253-1258 ◽  
Author(s):  
Karyn M. Austin ◽  
Rebecca J. Leary ◽  
Akiko Shimamura
Keyword(s):  
Bone Marrow Failure ◽  
Pancreatic Insufficiency ◽  
Intracellular Localization ◽  
Gene Mutations ◽  
Exocrine Pancreatic Insufficiency ◽  
Nucleolar Localization ◽  
Shwachman Diamond Syndrome ◽  
Low Levels ◽  
Cycle Dependent ◽  
Novel Protein

AbstractShwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The gene for this syndrome, SBDS, encodes a highly conserved novel protein. We characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and intracellular localization in 7 patients with SDS and healthy controls. As predicted by gene mutation, 4 patients with SDS exhibited no detectable full-length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T>C splice donor mutation, expressed scant levels of SBDS protein. Patient SD101 expressed low levels of SBDS protein harboring an R169C missense mutation. Patient DF269, who carried no detectable gene mutations, expressed wild-type levels of SBDS protein to add further support to the growing body of evidence for additional gene(s) that might contribute to the pathogenesis of the disease phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of normal control fibroblasts, but was particularly concentrated within the nucleolus. SBDS localization was cell-cycle dependent, with nucleolar localization during G1 and G2 and diffuse nuclear localization during S phase. SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar localization of SBDS provides further supportive evidence for its postulated role in rRNA processing.

scholarly journals A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations

2017 ◽  
Vol 55 (4) ◽  
pp. 3477-3489 ◽  
Author(s):  
Shaghayegh Taghavi ◽  
Rita Chaouni ◽  
Abbas Tafakhori ◽  
Luis J. Azcona ◽  
Saghar Ghasemi Firouzabadi ◽  
...  
Keyword(s):  
Genetic Study ◽  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Molecular Genetic Study ◽  
Novel Gene

scholarly journals Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome

2020 ◽  
Vol 21 (15) ◽  
pp. 5483 ◽  
Author(s):  
Gabriela Gajek ◽  
Anna S. Świerzko ◽  
Maciej Cedzyński
Keyword(s):  
Autosomal Recessive ◽  
Essential Role ◽  
Cleft Lip ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
Craniofacial Abnormalities ◽  
Radioulnar Synostosis ◽  
Mannose Binding ◽  
Cleft Lip Palate ◽  
Binding Lectin

The Malpuech, Michels, Mingarelli, Carnevale (3MC) syndrome is a rare, autosomal recessive genetic- disorder associated with mutations in the MASP1/3, COLEC1,1 or COLEC10 genes. The number of 3MC patients with known mutations in these three genes reported so far remains very small. To date, 16 mutations in MASP-1/3, 12 mutations in COLEC11 and three in COLEC10 associated with 3MC syndrome have been identified. Their products play an essential role as factors involved in the activation of complement via the lectin or alternative (MASP-3) pathways. Recent data indicate that mannose-binding lectin-associated serine protease-1 (MASP-1), MASP-3, collectin kidney-1 (collectin-11) (CL-K1), and collectin liver-1 (collectin-10) (CL-L1) also participate in the correct migration of neural crest cells (NCC) during embryogenesis. This is supported by relationships between MASP1/3, COLEC10, and COLEC11 gene mutations and the incidence of 3MC syndrome, associated with craniofacial abnormalities such as radioulnar synostosis high-arched eyebrows, cleft lip/palate, hearing loss, and ptosis.

Rhinosinusitis in the Pediatric Patient with Cystic Fibrosis

2014 ◽  
Vol 10 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Christopher Fundakowski ◽  
Rosemary Ojo ◽  
Ramzi Younis
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Pediatric Patients ◽  
Surgical Intervention ◽  
Chronic Sinusitis ◽  
Genetic Disorder ◽  
Symptomatic Relief ◽  
Recurrence Rates ◽  
Polyp Recurrence ◽  
Sinonasal Polyposis

Cystic fibrosis (CF) is a common autosomal recessive genetic disorder where a deletion mutation and subsequent downstream alteration in transmembrane regulator proteins results in increased mucus viscosity. CF manifests clinically with chronic multisystem inflammation and recurrent infections. Nearly all children with CF have chronic sinusitis, and a large majority will have concurrent sinonasal polyposis. Chronic sinusitis and sinonasal polyposis in pediatric patients with CF can be managed conservatively initially, though most will fail medical management and require surgical intervention. Unfortunately, symptom resolution is marginal and polyp recurrence rates are high. Currently, no cure exists for CF and the mainstay of treatment is to provide symptomatic relief, and minimize disease morbidity.

scholarly journals Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series

2021 ◽  
Author(s):  
Annette Münch ◽  
Christoph Bührer ◽  
Ann Carolin Longardt
Keyword(s):  
Weight Gain ◽  
Preterm Infants ◽  
Digestive Enzyme ◽  
Pancreatic Insufficiency ◽  
Growth Failure ◽  
Exocrine Pancreatic Function ◽  
Exocrine Pancreatic Insufficiency ◽  
Very Preterm Infants ◽  
Enzyme Replacement ◽  
Fecal Pancreatic Elastase

AbstractIn orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 μg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg−1 d−1. Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 μg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6–22.4] g kg−1 d−1 to 17.4 [8.4–29.0] g kg−1 d−1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02–0.13] g kcal−1 d−1 to 0.11 [0.05–0.18] g kcal−1 d−1.Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known:• Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function.• Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants.What is New:• Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain.• Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure.

Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families

2021 ◽  
pp. bjophthalmol-2020-318204
Author(s):  
Zohra Chibani ◽  
Imen Zone Abid ◽  
Peter Söderkvist ◽  
Jamel Feki ◽  
Mounira Hmani Aifa
Keyword(s):  
Autosomal Recessive ◽  
Corneal Transplantation ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Corneal Dystrophy ◽  
Solute Carrier Family ◽  
Transporter Protein ◽  
Bicarbonate Transporter ◽  
Corneal Clouding ◽  
Solute Carrier

BackgroundAutosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).MethodsTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.ResultsA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.ConclusionTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110065
Author(s):  
Nesrin Şenbil ◽  
Zeynep Arslan ◽  
Derya Beyza Sayın Kocakap ◽  
Yasemin Bilgili
Keyword(s):  
Corpus Callosum ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
Hirschsprung Disease ◽  
Agenesis Of Corpus Callosum ◽  
Whole Exome ◽  
Congenital Cardiac Anomalies ◽  
History Of ◽  
Gene Mutation Analysis

Mowat–Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ‘‘M’’ shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.

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