scholarly journals Genetics of alkaptonuria – an overview

2015 ◽  
Vol 62 (s11) ◽  
pp. 27-32
Author(s):  
Andrea Zatkova ◽  
Martina Nemethova
Keyword(s):  
Inborn Error ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Homogentisic Acid ◽  
Compound Heterozygous ◽  
Ochronotic Arthropathy ◽  
Pathogenic Variants ◽  
Gene Coding ◽  
Metabolic Block ◽  
Rare Autosomal Recessive Disease

Abstract Alkaptonuria (AKU) is the first described inborn error of metabolism and a classical example of rare autosomal recessive disease. AKU patients carry homozygous or compound heterozygous mutations of the gene coding for enzyme homogentisate dioxygenase (HGD) involved in metabolism of tyrosine. The metabolic block in AKU causes accumulation of homogentisic acid (HGA) that, with advancing age of the patient, leads to severe and painful ochronotic arthropathy. HGD gene was mapped to chromosome 3q13.3 and is composed of 14 exons. In about 400 patients, 142 pathogenic variants were reported that are listed in HGD mutations database (http://hgddatabase.cvtisr.sk/). In this review, we summarise different aspects of AKU genetics and impact of the HGD variants on enzyme function.

scholarly journals MCAD deficiency caused by compound heterozygous pathogenic variants in ACADM

2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Fumikatsu Nohara ◽  
Go Tajima ◽  
Hideo Sasai ◽  
Yoshio Makita
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Residual Activity ◽  
Complete Loss ◽  
Compound Heterozygous ◽  
Limit Of Quantification ◽  
Mcad Deficiency ◽  
Pathogenic Variants ◽  
Chain Acyl ◽  
Acyl Coenzyme A

AbstractMedium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is an autosomal recessive disease caused by biallelic pathogenic ACADM variants. We report a case of an asymptomatic Japanese girl with MCAD deficiency caused by compound heterozygous pathogenic variants (NM_000016.5:c.1040G > T (p.Gly347Val) and c.449_452delCTGA (p.Thr150ArgfsTer4)). Because the MCAD residual activity in lymphocytes of the patient was below the limit of quantification, both variants are likely to cause complete loss of MCAD enzymatic activity.

scholarly journals Combination of Novel c.3484G> T/p.Glu162Ter Variant in ABCB11 and c.208G> A/p.Asp70Asn Variant in ATP8B1 Are Associated with Severe Symptoms in Progressive Family Intrahepatic Cholestasis

2020 ◽  
Vol 09 (04) ◽  
pp. 285-288
Author(s):  
Mervan Bekdas ◽  
Guray Can ◽  
Recep Eroz ◽  
Selma Erdogan Duzcu
Keyword(s):  
Intrahepatic Cholestasis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Bile Secretion ◽  
Peripheral Blood Sample ◽  
Portal Fibrosis ◽  
Traditional Treatment ◽  
Pathogenic Variants ◽  
Chronic Cholestasis ◽  
Whole Exome

AbstractProgressive family intrahepatic cholestasis (PFIC) is an autosomal recessive disease that causes chronic cholestasis. It is associated with pathogenic variants in genes that encode proteins involved in bile secretion to canaliculus from hepatocytes. In this study, we present a 16-year-old boy who presented with severe pruritus and cholestatic jaundice. All possible infectious etiologies were negative. A liver biopsy was consistent with intrahepatic cholestasis and portal fibrosis. DNA was isolated from a peripheral blood sample, and whole exome sequencing was performed. A novel c.3484G > T/p.Glu162Ter variant in the ABCB11 gene and a c.208G> A/p.Asp70Asn variant in the ATP8B1 gene were detected. Despite traditional treatment, the patient's recurrent severe symptoms did not improve. The patient was referred for a liver transplantation. This novel c.3484G > T/p.Glu162Ter variant is associated with a severe and recurrent presentation, and the two compound variants could explain the severity of PFIC.

scholarly journals Rab27a

2001 ◽  
Vol 152 (4) ◽  
pp. 843-850 ◽  
Author(s):  
Philippe Bahadoran ◽  
Edith Aberdam ◽  
Frédéric Mantoux ◽  
Roser Buscà ◽  
Karine Bille ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Vesicle Transport ◽  
Myosin V ◽  
Griscelli Syndrome ◽  
V Gene ◽  
Rare Autosomal Recessive Disease ◽  
Phenotypic Reversion

Normal pigmentation depends on the uniform distribution of melanin-containing vesicles, the melanosomes, in the epidermis. Griscelli syndrome (GS) is a rare autosomal recessive disease, characterized by an immune deficiency and a partial albinism that has been ascribed to an abnormal melanosome distribution. GS maps to 15q21 and was first associated with mutations in the myosin-V gene. However, it was demonstrated recently that GS can also be caused by a mutation in the Rab27a gene. These observations prompted us to investigate the role of Rab27a in melanosome transport. Using immunofluorescence and immunoelectron microscopy studies, we show that in normal melanocytes Rab27a colocalizes with melanosomes. In melanocytes isolated from a patient with GS, we show an abnormal melanosome distribution and a lack of Rab27a expression. Finally, reexpression of Rab27a in GS melanocytes restored melanosome transport to dendrite tips, leading to a phenotypic reversion of the diseased cells. These results identify Rab27a as a key component of vesicle transport machinery in melanocytes.

Mutations in BTD gene causing biotinidase deficiency: a regional report

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Çiğdem Seher Kasapkara ◽  
Melek Akar ◽  
Mehmet Nuri Özbek ◽  
Heybet Tüzün ◽  
Bedri Aldudak ◽  
...  
Keyword(s):  
Inborn Error ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Biotinidase Deficiency ◽  
Compound Heterozygous ◽  
Metabolic Abnormalities ◽  
Base Pairs ◽  
Cutaneous Manifestations ◽  
Toxic Metabolites ◽  
Untreated Individuals

AbstractBiotinidase deficiency is an autosomal recessive inborn error of biotin metabolism. Children with biotinidase deficiency cannot cleave biocytin and, therefore, cannot recycle biotin. Untreated individuals become secondarily biotin deficient, which in turn results in decreased activities of the biotin-dependent carboxylases and the subsequent accumulation of toxic metabolites causing clinical symptoms. Biotinidase deficiency is characterized by neurological, cutaneous manifestations and metabolic abnormalities. The worldwide incidence of profound biotinidase deficiency has been estimated at 1:112,271. The human biotinidase gene is located on chromosome 3p25 and consists of four exons with a total length of 1629 base pairs. To date, more than 100 mutations in the biotinidase gene known to cause biotinidase deficiency have been reported. The vast majority of mutations are homozygous or compound heterozygous. Finding known mutations can be correlated with the biochemical enzymatic results. This report summarizes the demographic features of patients identified as biotinidase deficient from August of 2012 through August of 2013 and mutation analysis results for 20 cases in the southeast region of Turkey.

scholarly journals Acitretin Treatment for Lipoid Proteinosis

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Özgür Gündüz ◽  
Neriman Şahiner ◽  
Pınar Atasoy ◽  
Çağrı Şenyücel
Keyword(s):  
Respiratory Tract ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Clinical Importance ◽  
Histological Evaluation ◽  
Upper Respiratory Tract ◽  
Cutaneous Lesions ◽  
Lipoid Proteinosis ◽  
Upper Respiratory ◽  
Rare Autosomal Recessive Disease

Lipoid proteinosis (LP) is a rare, autosomal-recessive disease characterized by the hoarseness and widespread cutaneous scarring, more prominent on sun-exposed areas. Yellow-white plaques can be seen on oral mucosa and on the skin among depressed scars. Histological evaluation of the affected sites shows accumulation of hyaline-like material in dermis and disruption of basement membrane. Although LP is compatible with normal life expectancy, involvement of upper respiratory tract may endanger patient's life, especially in the case of a respiratory tract infection. Involvement of central nervous system has also been reported, but its clinical importance is obscure. Due to the rarity of LP, a definite therapeutical approach is not established. In this paper we describe a 21-year-old LP patient who was treated with acitretin for six months. Although the outcome with cutaneous lesions was not satisfactory, her hoarseness was significantly improved.

Rapid and Easy Diagnosis of Netherton Syndrome with Dermoscopy

2014 ◽  
Vol 18 (4) ◽  
pp. 280-282 ◽  
Author(s):  
Zeynep Meltem Akkurt ◽  
Tuba Tuncel ◽  
Erhan Ayhan ◽  
Derya Uçmak ◽  
Ünal Uluca ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Hair Shaft ◽  
Netherton Syndrome ◽  
Ichthyosis Linearis Circumflexa ◽  
Rare Autosomal Recessive Disease

Background: Netherton syndrome is a rare autosomal recessive disease demonstrating ichthyosis linearis circumflexa, atopic findings, and hair shaft anomalies. Trichorrhexis invaginata is the pathognomonic hair shaft anomaly seen in this syndrome. Objective: In recent years, hair shaft anomalies have been described as “matchstick” and “golf tee” signs. We present a patient with Netherton syndrome diagnosed by the presence of matchstick and golf tee hairs in addition to trichorrhexis invaginata.

scholarly journals Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

2021 ◽  
pp. 98-98
Author(s):  
Bojana Dobric ◽  
Danijela Radivojevic ◽  
Jovana Jecmenica ◽  
Vassos Neocleous ◽  
Pavlos Fanis ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Phenotype Correlation ◽  
Pathogenic Variants ◽  
Environmental Causes ◽  
35Delg Mutation

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.

scholarly journals Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: The first four patients in Serbia

2010 ◽  
Vol 138 (5-6) ◽  
pp. 351-355 ◽  
Author(s):  
Amira Peco-Antic ◽  
Martin Konrad ◽  
Gordana Milosevski-Lomic ◽  
Nikola Dimitrijevic
Keyword(s):  
Renal Failure ◽  
Secondary School ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Index Case ◽  
Serum Magnesium ◽  
Magnesium Supplementation ◽  
Moderate Renal Failure ◽  
Severe Growth ◽  
Rare Autosomal Recessive Disease

Introduction Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disease characterized by excessive renal magnesium and calcium wasting, bilateral nehrocalcinosis and progressive renal failure. This is the first report of FHHNC of four patients in Serbia. Outline of Cases The first three patients were siblings from the same family. The index case, a 9-yearold girl, presented with severe growth retardation, polyuria and polydipsia, while her brothers, 11 and 7 years old, were disclosed during family member screening. The father had a urolithiasis when aged 18 years, while intermittent microhaematuria and bilateral microlithiasis persisted later on. The fourth patient, a 16-year-old boy with sporadic FHHNC was discovered to have increased proteinuria at routine examination of urine before registration for secondary school. He was well grown up, normotensive, but had moderate renal failure (CKD 3 stage), mild hypomagnesaemia and severe hypercalciuria and nephrocalcinosis. Beside typical clinical and biochemical data, the diagnosis of FHHNC was confirmed by mutation analysis of the CLDN16 gene; in all four affected individuals a homozygous CLDN16 mutation (Leu151Phe) was found. Treatment with magnesium supplementation resulted in the normalization of serum magnesium levels only in one patient (patient 4), but hypercalciuria persisted and renal failure progressed in all patients. Conclusion FHHNC is a rare cause of chronic renal failure. The first four patients with FHHNC in Serbia have been here described. The diagnosis of FHNNC based on the findings of nephrocalcinosis with hypomagnesiaemia and hypercalciuria, was confirmed by homozygous paracellin1-mutation exhibiting a Leu151Phe. .

scholarly journals Infantile Sandhoff's disease

2009 ◽  
Vol 13 (3) ◽  
pp. 66 ◽  
Author(s):  
K Sass ◽  
S Wiebe ◽  
E Lemire
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Radiological Features ◽  
Rare Autosomal Recessive Disease ◽  
Case Based

Case based review of the rare autosomal recessive disease. Clinical and Radiological features described in detail.

CONGENITAL AFIBRINOGENAEMIA: DIAGNOSIS, CLINICAL FEATURES, FOLLOW-UP STUDY

1987 ◽  
Author(s):  
A M JakloyazAy ◽  
Oa H dnagy
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Renal Calculi ◽  
Bleeding Tendency ◽  
Fresh Blood ◽  
Severe Injuries ◽  
Surgical Interventions ◽  
Follow Up Study ◽  
Rare Autosomal Recessive Disease

Authors followed 6 cases of congenital afibrinogenae- mia (CA) by offsprings of two apparently unrelated families from the same village. The sex ratio was4.m/3.f. CA is a rare autosomal recessive disease. Controlling 76 family members authors detected 11 cases of moderate and 2 cases of severe hypofibrinogeneemia.Among them-without any bleeding tendency-the mother of one case and both parents of two siblings with CA*The lack of fibrinogen was confirmed biochemically and immunologically too. The only symptom ofthe Illness are the severe posttraumatic bleeding. They appear as epistax- is, bleeding of the gums, or anyother bleeding aiter minor or severe injuries*Intraarticular bleeding, as in haemophilia rarely occurs inCA. One of our patients had profuse haematurias, causedby renal calculi. The only therapy is the substitution with transfusions of fresh blood, plasma, or fibrinogen concentrates*The rise of posttransfusional lllnisses grows with the number of transfusions*Stomatological or surgical interventions could be performed only after correction of the dotting abnormalitySo, one of our patients was submitted to splenectomyfor spontaneous rupture at 12 years and to nephrectomy for severe pyelo-caliceal cal- culosis with 19.He recovered fully after both interventions but died at 21 years after a bicycle accidenti The five other patients deceased at the age of 5«resp. 10 months and at 6-lo-resp 12 years. In 3 cases there was a subdural hammorrhage, once an intracranial blee- dingCnon autopsiated)and once a severe intraabdoml- nal haemorrhage after an accidental traumatism of the abdominal wall. The care of the CA cases is mostly a pediatric proble. The frequency of the pottraumatic bleeding decrease with the growth*The schoolchildren are paying more attention to avoid injuries

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