scholarly journals Papillion-Lefèvre Syndrome: Periodontists’ Perspective

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Sunil Kumar Biraggari ◽  
K. Krishna Mohana Reddy ◽  
J. Sudhakar ◽  
Shiva Shankar Bugude ◽  
Rajesh Nichenametla ◽  
...  
Keyword(s):  
Gene Locus ◽  
Autosomal Recessive ◽  
Major Gene ◽  
Autosomal Recessive Inheritance ◽  
Signs And Symptoms ◽  
Loss Of Function ◽  
Gingival Inflammation ◽  
Deciduous Dentition ◽  
Genetic Studies ◽  
Present Case Report

Papillion-Lefèvre Syndrome is a very rare disorder of autosomal recessive inheritance distinguished by palmar plantar hyperkeratosis and early onset of periodontitis affecting the dentition. Genetic studies have identified a mutation in the major gene locus of chromosome 11q14 with loss of function. Cathepsin C gene is to be responsible for Papillion-Lefèvre Syndrome. The present case report describes a 13-year-old female, who visited the Department of Periodontology with the chief compliant of bleeding gums and loose teeth. She presented with the signs and symptoms of Papillion-Lefèvre Syndrome. The patient had premature shedding of her deciduous dentition. On clinical examination, extraorally, the patient presented with persistent thickening, flaking, and scaling of the skin of palms and soles. Her intraoral examination revealed gingival inflammation, abscess formation, and periodontal pockets. Her intraoral radiographs showed bone loss involving the central incisors and molars. The patient underwent periodontal therapy and is under maintenance.

scholarly journals Papillon Lefevre Syndrome: Diagnosis and Management in Two Affected Siblings – A Case Report

2020 ◽  
Vol 29 (04) ◽  
pp. 264-268
Author(s):  
Abul Khair Zalan ◽  
◽  
Khadeejah Khalil Zubairy ◽  
Anser Maxood ◽  
Manahil Niazi ◽  
...  
Keyword(s):  
Case Report ◽  
Autosomal Recessive ◽  
Major Gene ◽  
Autosomal Recessive Disorder ◽  
Permanent Teeth ◽  
Loss Of Function ◽  
Genetic Studies ◽  
Diagnosis And Management ◽  
Syndrome Diagnosis ◽  
Dent Assoc

Papillon-Lefèvre syndrome (PLS) an autosomal recessive disorder characterized by diffuse transgradient palmar-plantar hyperkeratosis, with premature loss of deciduous and permanent teeth, along with the calcification of the dura mater. This results in teeth radiographically appearing as “floating” in the soft tissue. Genetic studies of patients with PLS have mapped the major gene locus to chromosome 11q24-q21 and revealed mutation and loss of function of the cathepsin gene. It affects 1- 4 people per 1 million population with no gender or racial predilection. Dermatological manifestations, usually occurs before four years of age, include hyperkeratosis of palms and soles, nail dystrophy, hyperhidrosis and keratinization on elbows and knees with the lesions appearing as white, yellow-like or red plaques or patches that then develop cracks, crusts, or deep fissures. KEYWORD: Papillon-lefevre syndrome, hyperkeratosis HOW TO CITE: Zalan AK, Zubairy KK, Maxood A, Niazi M, Zaman H, Gul A, Anser M. Papillon lefevre syndrome: Diagnosis and management in two affected siblings – A case report. J Pak Dent Assoc 2020;29(4):264-268.

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

scholarly journals PRKG2 Splice Site Variant in Dogo Argentino Dogs with Disproportionate Dwarfism

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1489
Author(s):  
Gabriela Rudd Garces ◽  
Maria Elena Turba ◽  
Myriam Muracchini ◽  
Alessia Diana ◽  
Vidhya Jagannathan ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Donor Site ◽  
Genetic Defect ◽  
Autosomal Recessive Inheritance ◽  
Homozygosity Mapping ◽  
Splice Donor Site ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Encoding Protein

Dwarfism phenotypes occur in many species and may be caused by genetic or environmental factors. In this study, we investigated a family of nine Dogo Argentino dogs, in which two dogs were affected by disproportionate dwarfism. Radiographs of an affected dog revealed a decreased level of endochondral ossification in its growth plates, and a premature closure of the distal ulnar physes. The pedigree of the dogs presented evidence of monogenic autosomal recessive inheritance; combined linkage and homozygosity mapping assigned the most likely position of a potential genetic defect to 34 genome segments, totaling 125 Mb. The genome of an affected dog was sequenced and compared to 795 control genomes. The prioritization of private variants revealed a clear top candidate variant for the observed dwarfism. This variant, PRKG2:XM_022413533.1:c.1634 + 1G>T, affects the splice donor site and is therefore predicted to disrupt the function of the PKRG2 gene encoding protein, kinase cGMP-dependent type 2, a known regulator of chondrocyte differentiation. The genotypes of the PRKG2 variant were perfectly associated with the phenotype in the studied family of dogs. PRKG2 loss-of-function variants were previously reported to cause disproportionate dwarfism in humans, cattle, mice, and rats. Together with the comparative data from other species, our data strongly suggest PRKG2:c.1634+1G>T to be a candidate causative variant for the observed dwarfism phenotype in Dogo Argentino dogs.

scholarly journals Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Ghazanfar Ali ◽  
Sadia ◽  
Jia Nee Foo ◽  
Abdul Nasir ◽  
Chu-Hua Chang ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Clinical Feature ◽  
Illumina Hiseq ◽  
Genetic Studies ◽  
Bardet Biedl Syndrome ◽  
Whole Exome ◽  
Kashmiri Population ◽  
Renal Abnormalities

Background. Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. Methods. The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. Results. WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. Conclusion. Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.

scholarly journals SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia

2020 ◽  
Vol 6 (4) ◽  
pp. e478 ◽  
Author(s):  
Tommy Stödberg ◽  
Måns Magnusson ◽  
Nicole Lesko ◽  
Anna Wredenberg ◽  
Daniel Martin Munoz ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Neurodevelopmental Disorder ◽  
Brain Mri ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Inheritance Pattern ◽  
Loss Of Function ◽  
Pathogenic Variants ◽  
Gastrointestinal Problems ◽  
Life Threatening

ObjectiveTo describe the phenotype in 2 sisters with a rare constellation of neurologic symptoms and secretory impairments and to identify the etiology by the use of whole-genome sequencing (WGS).MethodsAfter an extensive workup failed to reveal the cause of disease, in a girl with a previously not reported phenotype, WGS of the proband, her diseased older sister, an older healthy brother, and their parents was performed, and potentially pathogenic variants were analyzed.ResultsThe proband and her older sister both presented with neonatal Staphylococcus aureus parotitis, apneas, disappearance of the Moro reflex, and hypotonia. The proband survived. Her brain MRI showed white matter and basal ganglia abnormalities, and CSF damage biomarkers were increased. At age 8 years, she exhibits a constellation of symptoms including severe neurodevelopmental disorder, hearing impairment, gastrointestinal problems, and a striking lack of tear fluid, saliva, and sweat. Her respiratory mucosa is dry with potentially life-threatening mucus plugging. Through WGS, 2 loss-of-function variants in SLC12A2 were identified that follow an autosomal recessive inheritance pattern.ConclusionsTaken together with a single previously reported case and the close resemblance to the phenotypes of corresponding mouse models, our study firmly establishes biallelic variants in SLC12A2 as causing human disease and adds data regarding the neurologic phenotype.

scholarly journals Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

2020 ◽  
Vol 32 (1) ◽  
pp. 223-228
Author(s):  
Veronica Arora ◽  
Suliman Khan ◽  
Ayman W. El-Hattab ◽  
Ratna Dua Puri ◽  
Maria Eugenia Rocha ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Renal Agenesis ◽  
Genetic Diagnosis ◽  
Hirschsprung Disease ◽  
Autosomal Recessive Inheritance ◽  
Causal Role ◽  
Data Repository ◽  
Loss Of Function ◽  
Genome Data ◽  
Fatal Form

BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) are one of the most common malformations identified in the fetal stage. Bilateral renal agenesis (BRA) represents the most severe and fatal form of CAKUT. Only three genes have been confirmed to have a causal role in humans (ITGA8, GREB1L, and FGF20).MethodsGenome sequencing within a diagnostic setting and combined data repository analysis identified a novel gene.ResultsTwo patients presented with BRA, detected during the prenatal period, without additional recognizable malformations. They had parental consanguinity and similarly affected, deceased siblings, suggesting autosomal recessive inheritance. Evaluation of homozygous regions in patient 1 identified a novel, nonsense variant in GFRA1 (NM_001348097.1:c.676C>T, p.[Arg226*]). We identified 184 patients in our repository with renal agenesis and analyzed their exome/genome data. Of these 184 samples, 36 were from patients who presented with isolated renal agenesis. Two of them had loss-of-function variants in GFRA1. The second patient was homozygous for a frameshift variant (NM_001348097.1:c.1294delA, p.[Thr432Profs*13]). The GFRA1 gene encodes a receptor on the Wolffian duct that regulates ureteric bud outgrowth in the development of a functional renal system, and has a putative role in the pathogenesis of Hirschsprung disease.ConclusionsThese findings strongly support the causal role of GFRA1-inactivating variants for an autosomal recessive, nonsyndromic form of BRA. This knowledge will enable early genetic diagnosis and better genetic counseling for families with BRA.

scholarly journals A Novel Loss-of-Function Mutation, Gln459Arg, of the Calcium-Sensing Receptor Gene Associated with Apparent Autosomal Recessive Inheritance of Familial Hypocalciuric Hypercalcemia

2009 ◽  
Vol 94 (11) ◽  
pp. 4372-4379 ◽  
Author(s):  
Steven A. Lietman ◽  
Yardena Tenenbaum-Rakover ◽  
Tjin Shing Jap ◽  
Wu Yi-Chi ◽  
Yang De-Ming ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Biochemical Characterization ◽  
Autosomal Recessive Inheritance ◽  
Recessive Inheritance ◽  
Familial Hypocalciuric Hypercalcemia ◽  
Loss Of Function ◽  
Calcium Sensing Receptor ◽  
Casr Gene ◽  
Calcium Sensing ◽  
Inactivating Mutation

Context: Mutations that inactivate one allele of the gene encoding the calcium sensing receptor (CaSR) cause autosomal dominant familial hypocalciuric hypercalcemia (FHH), whereas homozygous mutations cause neonatal severe hyperparathyroidism. Objective: We describe the identification and biochemical characterization of a novel CASR gene mutation that caused apparent autosomal recessive FHH in an extended consanguineous kindred. Design: The study design involved direct sequence analysis of the CaSR gene, clinical and biochemical analyses of patients, and in vitro immunobiochemical studies of the mutant CaSR. Results: A novel inactivating mutation (Q459R) was identified in exon 4 of both alleles of the CASR in the proband, who presented with asymptomatic hypercalcemia and hypocalciuria at age 2 yr. The proband’s parents were heterozygous for the Q459R mutation consistent with autosomal recessive inheritance of FHH. Among 13 family members that were studied, eight subjects were heterozygous for the Q459R mutation and five had normal genotypes. All heterozygous subjects were asymptomatic and normocalcemic apart from one subject who was mildly hypercalcemic. The Q459R mutant CaSR was normally expressed at the cell membrane but retained only 30–50% of the calcium-dependent activity of the wild-type CaSR. Conclusion: We identified a novel loss-of-function Q459R mutation in the CASR gene that exhibits mildly reduced sensitivity to calcium and that is associated with apparent autosomal recessive transmission of FHH. This study demonstrates the importance of genetic testing in FHH to distinguish between de novo and inherited mutations of the CASR gene and assist in management decisions. An extended kindred with familial hypocalciuric hypercalcemia possessed a novel inactivating mutation of the CaSR with highly variable biochemical phenotypes and apparent autosomal recessive inheritance.

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