Renal Failure Associated with APECED and Terminal 4q Deletion: Evidence of Autoimmune Nephropathy

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes' response toCandida albicansat 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH.AIREfull gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.

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

Journal of Pediatric Genetics ◽

10.1055/s-0040-1719161 ◽

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.

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

Journal of Alzheimer s Disease ◽

10.3233/jad-201085 ◽

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.

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Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000800012 ◽

2008 ◽

Vol 52 (8) ◽

pp. 1277-1281 ◽

Cited By ~ 8

Author(s):

Fernanda Borchers Coeli ◽

Lúcio Fábio Caldas Ferraz ◽

Sofia H. V. de Lemos-Marini ◽

Sumara Zuanazi Pinto Rigatto ◽

Vera Maria Santoro Belangero ◽

...

Keyword(s):

Mineralocorticoid Receptor ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

Molecular Studies ◽

Apparent Mineralocorticoid Excess ◽

Gene Maps ◽

Apparent Mineralocorticoid Excess Syndrome

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0018 ◽

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.

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

Frontiers in Genetics ◽

10.3389/fgene.2021.726116 ◽

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.

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Mitochondrial Neurogastrointestinal Encephalomyopathy Disease in Three Siblings from Pakistan with a Novel Mutation

Journal of Pediatric Genetics ◽

10.1055/s-0038-1661411 ◽

2018 ◽

Vol 08 (01) ◽

pp. 015-019

Author(s):

Sana Durrani ◽

Bee Chen ◽

Yusnita Yakob ◽

Lua Hian ◽

Bushra Afroze

Keyword(s):

Thymidine Phosphorylase ◽

Autosomal Recessive ◽

Novel Mutation ◽

Gastrointestinal Symptoms ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

Pakistani Family ◽

Mitochondrial Neurogastrointestinal Encephalomyopathy ◽

Intestinal Dysmotility ◽

Sensorineural Hearing Impairment

AbstractMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare multisystem autosomal recessive disorder. The disease is clinically heterogeneous with gastrointestinal symptoms of intestinal dysmotility and cachexia as well as neurological symptoms of ophthalmoplegia, neuropathy, sensorineural hearing impairment, and diffuse leukoencephalopathy being most prominent. MNGIE is caused by mutations in TYMP, a gene that encodes thymidine phosphorylase (TP)—a cytosolic enzyme. Mutations in TYMP lead to very low TP catalytic activity, resulting in dramatically increased thymidine and deoxyuridine in plasma. We describe the clinical, biochemical, and neuroimaging findings of three boys with MNGIE from a Pakistani family with a novel homozygous mutation, c.798_801dupCGCG p. (Ala268Argfs*?), in exon 7 of TYMP.

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Cockayne Syndrome with ERCC8 Gene Mutation: A Case Report

Bangladesh Journal of Child Health ◽

10.3329/bjch.v44i3.52713 ◽

2021 ◽

Vol 44 (3) ◽

pp. 181-183

Author(s):

Kanij Fatema ◽

Md Mizanur Rahman ◽

Shaheen Akhter

Keyword(s):

Case Report ◽

Autosomal Recessive ◽

Genetic Disorder ◽

Growth Failure ◽

Autosomal Recessive Disorder ◽

Cockayne Syndrome ◽

Global Developmental Delay ◽

Hearing Disorders ◽

Cognitive Delay ◽

Intracerebral Calcification

Cockayne syndrome (CS) is a genetic disorder characterized by growth failure, microcephaly, cognitive delay, visual and hearing disorders. Patients usually present with dysmorphism and global delay. It is an autosomal recessive disorder, mutation of two genes ERCC8 and ERCC6 were observed. We report a 4 year old child who was diagnosed as a case of Cockayne syndrome, based on clinical, neuroimaging and genetic study findings. This case had growth failure, dysmorphism, optic atrophy, global developmental delay, intracerebral calcification and mutation of ERCC8 gene. Bangladesh J Child Health 2020; VOL 44 (3) :181-183

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A novel ALMS1 homozygous mutation in two Turkish brothers with Alström syndrome

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0249 ◽

2016 ◽

Vol 29 (5) ◽

Cited By ~ 1

Author(s):

Caley Laxer ◽

Sofia A. Rahman ◽

Maha Sherif ◽

Sophia Tahir ◽

Atilla Cayir ◽

...

Keyword(s):

Autosomal Recessive ◽

Novel Mutation ◽

Autosomal Recessive Disorder ◽

Homozygous Mutation ◽

Consanguineous Family ◽

Complex Phenotype ◽

Rare Autosomal Recessive Disorder ◽

Alström Syndrome ◽

Alstrom Syndrome

AbstractAlström syndrome (AS) is an extremely rare, autosomal recessive disorder characterised by multi-organ features that typically manifest within the first two decades of life. AS is caused by mutations in the Alström syndrome 1 (In the current study, two brothers from a first-cousin consanguineous family presented with a complex phenotype and were suspected of having AS.Both brothers were found to be homozygous for a novel nonsense c.7310C>A (p.S2437X) mutation in exon-8 ofThis particular mutation has never been reported before and confirmed the diagnosis of AS in the patients. Our work identifies a novel mutation in

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A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia

Thrombosis and Haemostasis ◽

10.1160/th12-12-0934 ◽

2013 ◽

Vol 110 (07) ◽

pp. 76-82 ◽

Cited By ~ 1

Author(s):

Ziqiang Yu ◽

Lijuan Cao ◽

Wei Zhang ◽

Xia Bai ◽

Changgeng Ruan ◽

...

Keyword(s):

Autosomal Recessive ◽

Frameshift Mutation ◽

Culture Media ◽

Autosomal Recessive Disorder ◽

Immunological Methods ◽

Homozygous Mutation ◽

Wild Type ◽

Exon 2 ◽

Molecular Analyses ◽

Bleeding Episodes

SummaryCongenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.

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Meckel Gruber Syndrome: a rare case report

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20175598 ◽

2017 ◽

Vol 5 (1) ◽

pp. 262

Author(s):

Manish Verma ◽

Shruti Sharma ◽

Kiran Suthar ◽

Beena Thada

Keyword(s):

Renal Failure ◽

Case Report ◽

Rare Case ◽

Autosomal Recessive ◽

Pulmonary Hypoplasia ◽

Autosomal Recessive Disorder ◽

Polycystic Kidneys ◽

Rare Autosomal Recessive Disorder ◽

Live Births ◽

Rare Case Report

Meckel gruber syndrome or dysencephalia splanchnocystica, is a rare autosomal recessive disorder caused by failure of mesodermal induction. Worldwide incidence of MGS is 1 per 13,500-140,000 live births. It is characterized by triad of occipital Meningoencephalocele, polycystic kidneys and post-axial polydactyly. Most fetuses affected with this syndrome die before birth due to oligohydramnios, renal failure or pulmonary hypoplasia. We report a rare case of MGS who delivered live at birth with classical features.

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