The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Enise Avci Durmusalioglu ◽  
Esra Isik ◽  
Durdugul Ayyildiz Emecen ◽  
Damla Goksen ◽  
Samim Ozen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Diagnostic Process ◽  
Homozygous Mutation ◽  
Lysinuric Protein Intolerance ◽  
Case Presentation ◽  
Lysinuric Protein ◽  
Next Generation Sequencing Ngs ◽  
Protein Intolerance ◽  
Generation Sequencing

Abstract Objectives Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping. Case presentation A fifteen-year-old-boy with an initial diagnosis of osteogenesis imperfecta, was referred due to a number of atypical findings accompanying to osteoporosis such as splenomegaly and bicytopenia. A NGS panel (TruSight One Sequencing Panel) was performed and a novel homozygous mutation of c.257G>A (p.Gly86Glu) in the SLC7A7 gene (NM_001126106.2), responsible for LPI, was detected. The diagnosis was confirmed via reverse phenotyping. Conclusions Reverse phenotyping using a multigene panel shortens the diagnostic process.

scholarly journals Cone Dystrophy in Patient with HomozygousRP1L1Mutation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sachiko Kikuchi ◽  
Shuhei Kameya ◽  
Kiyoko Gocho ◽  
Said El Shamieh ◽  
Keiichiro Akeo ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Cone Dystrophy ◽  
Homozygous Mutation ◽  
Full Field ◽  
Clinical Evaluations ◽  
Normal Visual Acuity ◽  
Severe Reduction ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Cone Density

The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygousRP1L1mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygousRP1L1mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of thePCDH15,RPGRIP1, andGPR98genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of theRP1L1homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in theRP1L1gene can cause cone dystrophy.

scholarly journals Case Report: Identification of a Novel Homozygous Mutation in GPD1 Gene of a Chinese Child With Transient Infantile Hypertriglyceridemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Haihua Lin ◽  
Youhong Fang ◽  
Lin Han ◽  
Jie Chen ◽  
Jingan Lou ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Underlying Mechanism ◽  
Causative Factor ◽  
Homozygous Mutation ◽  
Clinical Presentations ◽  
Chinese Girl ◽  
Gpd1 Gene ◽  
Generation Sequencing

Transient infantile hypertriglyceridemia is a rare autosomal recessive disorder characterized by hypertriglyceridemia, hypohepatia, hepatomegaly, hepatic steatosis and fibrosis in infancy. Mutations in GPD1 gene are considered the causative factor but the underlying mechanism of this disorder is still enigmatic. To date, only 24 different GPD1 mutations have been reported in the literature worldwide with transient infantile hypertriglyceridemia or relevant conditions. Here we report a Chinese girl who developed hepatomegaly hepatic steatosis, elevated transaminase and hypertriglyceridemia from the age of 4 months. A novel homozygous variant c.454C>T (p.Q152*) was found in GPD1 gene by next-generation sequencing. This patient is the 3rd Asian reported with transient infantile hypertriglyceridemia. We summarized the clinical presentations of transient infantile hypertriglyceridemia and also expanded the spectrum of disease-causing mutations in GPD1.

Lysinuric protein intolerance, an autosomal recessive disease

2008 ◽  
Vol 2 (4) ◽  
pp. 214-222 ◽  
Author(s):  
R. Norio ◽  
J. Perheentupa ◽  
M. Kekomäki ◽  
J. K. Visakorpi
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

scholarly journals Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) using Next Generation Sequencing (NGS)

2021 ◽  
Author(s):  
Ioannis Papoulidis ◽  
Makarios Eleftheriades ◽  
Emmanouil Manolakos ◽  
Simoni Maria Liapi ◽  
Anastasia Konstantinidou ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Tandem Repeats ◽  
Novel Mutation ◽  
Homozygous Mutation ◽  
Primary Microcephaly ◽  
Strong Connection ◽  
C Terminus ◽  
Next Generation Sequencing Ngs ◽  
Autosomal Recessive Primary Microcephaly ◽  
Generation Sequencing

MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.

scholarly journals Lysinuric protein intolerance: an overlooked diagnosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Asburce Olgac ◽  
Idil Yenicesu ◽  
Rıza Köksal Ozgul ◽  
Gürsel Biberoğlu ◽  
Leyla Tümer
Keyword(s):  
Amino Acid ◽  
Complete Blood Count ◽  
Clinical Symptoms ◽  
Basolateral Membrane ◽  
Genetic Defect ◽  
Good Condition ◽  
Homozygous Mutation ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

Abstract Background Lysinuric protein intolerance (LPI) is an autosomal recessively inherited inborn error of metabolism (IEM) caused by the defect in the dibasic cationic amino acid transporter found on the basolateral membrane of the lung, small intestine, and kidney due to mutations in the SLC7A7 gene, which encodes the y+LAT1 protein. LPI may present as an acute hyperammonemic episode or as chronic symptoms. Major clinical symptoms are feeding problems, vomiting and diarrhea, failure to thrive, hepatosplenomegaly, and cytopenia. We present a delayed diagnosis of symptomatic LPI with a homozygous mutation in the SLC7A7 gene. Case presentation A 15-year-old girl was referred to our clinic due to growth retardation and diarrhea. Physical examination showed short stature, retarded puberty, and hepatosplenomegaly. Laboratory tests showed normal complete blood count and biochemical analyses except elevated aspartate aminotransferase, triglyceride, total cholesterol, and ferritin. Peripheral blood smear and hemoglobin electrophoresis were within normal limits. Bone marrow analysis showed hemophagocytic cells. Postprandial ammonium level was found elevated. Low lysine, arginine, and ornithine and elevated glycine and alanine in plasma amino acid analysis and high amount of lysine and slightly elevated arginine and ornithine excretion in urine were detected. Molecular genetic analysis of the SLC7A7 gene showed a previously reported homozygous mutation. Low protein diet, sodium benzoate, l-carnitine, low-dose l-citrulline, and calcium replacement were initiated. The patient is now in good condition still being followed up in our department. Conclusions LPI is a metabolic disorder with multi-systemic involvement that may have severe consequences if left untreated. Initiation of early treatment is essential for the prevention of severe chronic complications. Also, confirmation of the genetic defect may provide the parents to have healthy offsprings in the future with the help of genetic counselling and preimplantation genetics.

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.

SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance

10.1038/6815 ◽  
1999 ◽  
Vol 21 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Giuseppe Borsani ◽  
Maria Teresa Bassi ◽  
Maria Pia Sperandeo ◽  
Alessandro De Grandi ◽  
Anna Buoninconti ◽  
...  
Keyword(s):  
Related Protein ◽  
Lysinuric Protein Intolerance ◽  
Lysinuric Protein ◽  
Protein Intolerance

scholarly journals Severe pneumonia caused by Parvimonas micra: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qing Yu ◽  
Lingling Sun ◽  
Zuqing Xu ◽  
Lumei Fan ◽  
Yunbo Du
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Case Reports ◽  
Severe Pneumonia ◽  
Lavage Fluid ◽  
Due Date ◽  
Case Presentation ◽  
Abdominal Abscesses ◽  
Parvimonas Micra ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background Parvimonas micra (P. micra) is a gram-positive anaerobic coccus that is detected widely on the skin, in the oral mucosa and in the gastrointestinal tract. In certain circumstances, P. micra can cause abdominal abscesses, bacteraemia and other infections. To the best of our knowledge, there have been no case reports describing the biological characteristics of P. micra-related pneumonia. These bacteria do not always multiply in an aerobic organ, such as the lung, and they could be easily overlooked because of the clinical mindset. Case presentation A 35-year-old pregnant woman was admitted to the emergency department 4 weeks prior to her due date who was exhibiting 5 points on the Glasgow coma scale. A computed tomography (CT) scan showed a massive haemorrhage in her left basal ganglia. She underwent a caesarean section and brain surgery before being admitted to the ICU. She soon developed severe pneumonia and hypoxemia. Given that multiple sputum cultures were negative, the patient’s bronchoalveolar lavage fluid was submitted for next-generation sequencing (NGS) to determine the pathogen responsible for the pneumonia; as a result, P. micra was determined to be the causative pathogen. Accordingly the antibiotic therapy was altered and the pneumonia improved. Conclusion In this case, we demonstrated severe pneumonia caused by the anaerobic organism P. micra, and the patient benefited from receiving the correct antibiotic. NGS was used as a method of quick diagnosis when sputum culture failed to distinguish the pathogen.

Neuropathological Alzheimer’s Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes

2021 ◽  
Vol 79 (1) ◽  
pp. 25-30
Author(s):  
Emanuela Maderna ◽  
Silvia Visonà ◽  
Vittorio Bolcato ◽  
Veronica Redaelli ◽  
Paola Caroppo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Recessive ◽  
Cerebral Atrophy ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
Neurofibrillary Changes ◽  
Axonal Spheroids ◽  
Temporal Structures ◽  
Cortical Involvement

Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer’s disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer’s disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.

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.

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