scholarly journals Autosomal Recessive Disorder Otospondylomegaepiphyseal Dysplasia Is Associated with Loss-of-Function Mutations in the COL11A2 Gene

2000 ◽  
Vol 66 (2) ◽  
pp. 368-377 ◽  
Author(s):  
Miia Melkoniemi ◽  
Han G. Brunner ◽  
Sylvie Manouvrier ◽  
Raoul Hennekam ◽  
Andrea Superti-Furga ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Loss Of Function ◽  
Col11a2 Gene

scholarly journals Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samina Yasin ◽  
Outi Makitie ◽  
Sadaf Naz
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Loss Of Function ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Skeletal Malformations ◽  
Tarsal Bones ◽  
The Family ◽  
Heterozygous Carriers

Abstract Background Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. Case presentation We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. Conclusion Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

scholarly journals SERKAL Syndrome: An Autosomal-Recessive Disorder Caused by a Loss-of-Function Mutation in WNT4

2008 ◽  
Vol 82 (1) ◽  
pp. 39-47 ◽  
Author(s):  
Hannah Mandel ◽  
Revital Shemer ◽  
Zvi U. Borochowitz ◽  
Marina Okopnik ◽  
Carlos Knopf ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Loss Of Function

scholarly journals Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1)

2012 ◽  
Vol 303 (6) ◽  
pp. C673-C681 ◽  
Author(s):  
Rongbao Zhao ◽  
Daniel Sanghoon Shin ◽  
Andras Fiser ◽  
I. David Goldman
Keyword(s):  
Functional Role ◽  
Autosomal Recessive ◽  
Structural Model ◽  
Transmembrane Domain ◽  
Autosomal Recessive Disorder ◽  
Binding Pocket ◽  
Loss Of Function ◽  
Substituted Cysteine Accessibility ◽  
Translocation Pathway

The proton-coupled folate transporter (PCFT) mediates intestinal folate absorption, and loss-of-function mutations in this gene result in the autosomal recessive disorder hereditary folate malabsorption. The current study, focused on a structure-functional analysis of this transporter, identified Gly-189 and Gly-192 (a GxxG motif) located in the fifth transmembrane domain as residues that could not be replaced with alanine without a loss of function. In contrast, function was preserved when Gly-56 and Gly-59 (the other conservative GXXG motif in human PCFT) were replaced with alanine. Similarly, Gly-93 and Gly-97, which constitute the only conserved GXXXG dimerization motif in human PCFT, tolerated alanine substitution. To explore the role of this region in folate binding, the residues around Gly-189 and Gly-192 were analyzed by the substituted cysteine accessibility method. Both I188C and M193C mutants were functional and were inhibited by membrane-impermeable sulfhydryl-reactive reagents; this could be prevented with PCFT substrate, but the protection was sustained at 0°C only for the I188C mutant, consistent with localization of Ile-188 in the PCFT folate binding pocket. The functional role of residues around Gly-189 and Gly-192 is consistent with a molecular structural model in which these two residues along with Ieu-188 are accessible to the PCFT aqueous translocation pathway.

scholarly journals A Novel Mutation in the VPS13B Gene in a Cohen Syndrome Patient with Positive Antiphospholipid Antibodies

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Roghayeh Dehghan ◽  
Mahdiyeh Behnam ◽  
Alireza Moafi ◽  
Mansoor Salehi
Keyword(s):  
Antiphospholipid Antibodies ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Mental Deficiency ◽  
Autosomal Recessive Disorder ◽  
Facial Features ◽  
Loss Of Function ◽  
Cohen Syndrome ◽  
Mild Anemia ◽  
Homozygous Nonsense Mutation

Cohen syndrome is an autosomal recessive disorder with the primary symptoms of mental deficiency, progressive retinopathy, hypotonia, microcephaly, obesity of midchildhood onset, intermittent neutropenia, and dysmorphic facial features. The syndrome has high phenotypic heterogeneity and is caused by loss-of-function mutations in the VPS13B gene. Here, we introduce a novel homozygous nonsense mutation (c.8698G > T, p.E2900X) in the VPS13B gene in an 11-year-old Iranian boy with major symptoms of Cohen syndrome. He also had mild anemia accompanied by positive antiphospholipid antibodies, the latter has never been previously reported in Cohen syndrome.

scholarly journals The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1147-1152 ◽  
Author(s):  
Rongbao Zhao ◽  
Sang Hee Min ◽  
Andong Qiu ◽  
Antoinette Sakaris ◽  
Gary L. Goldberg ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Amino Acid Residues ◽  
Loss Of Function ◽  
Folate Transport ◽  
Gene Encoding ◽  
Gene Coding ◽  
The Central Nervous System ◽  
Racial Ethnic

Abstract Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by impaired intestinal folate absorption and impaired folate transport into the central nervous system. Recent studies in 1 family revealed that the molecular basis for this disorder is a loss-of-function mutation in the PCFT gene encoding a proton-coupled folate transporter. The current study broadens the understanding of the spectrum of alterations in the PCFT gene associated with HFM in 5 additional patients. There was no racial, ethnic, or sex pattern. A total of 4 different homozygous mutations were detected in 4 patients; 2 heterozygous mutations were identified in the fifth patient. Mutations involved 4 of the 5 exons, all at highly conserved amino acid residues. A total of 4 of the mutated transporters resulted in a complete loss of transport function, primarily due to decreased protein stability and/or defects in membrane trafficking, while 2 of the mutated carriers manifested residual function. Folate transport at low pH was markedly impaired in transformed lymphocytes from 2 patients. These findings further substantiate the role that mutations in PCFT play in the pathogenesis of HFM and will make possible rapid diagnosis and treatment of this disorder in infants, and prenatal diagnosis in families that carry a mutated gene.

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.

Three Cases of Joubert Syndrome in a Consanguineous Syrian Family and a Interesting Case of Multinational Collaboration

2021 ◽  
Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed
Keyword(s):  
Low Income ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Joubert Syndrome ◽  
Interesting Case ◽  
Low Income Countries ◽  
Ocular Motor ◽  
Quality Health Care ◽  
Quality Health ◽  
Motor Apraxia

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.

A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene

2020 ◽  
Author(s):  
Hasan Akduman ◽  
Dilek Dilli ◽  
Serdar Ceylaner
Keyword(s):  
Mutation Analysis ◽  
Autosomal Recessive ◽  
Glucose Transporter ◽  
Neonatal Period ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
New Mutation ◽  
Early Neonatal Period ◽  
Sodium Dependent ◽  
Hypernatremic Dehydration

AbstractCongenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

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