Novel mutation in the RAB3GAP1 gene, the first diagnosed Warburg Micro syndrome case in Syria

Abstract Warburg Micro syndrome is a rare autosomal recessive disease due to mutation in the RAB3GAP1, RAB3GAP2, RAB18 and TBC1D20 genes. It is commonly seen in consanguineous marriages, characterized by optic (microcornea, microphthalmia, congenital cataracts), neurologic )microcephaly, corpus callosum hypoplasia, severe mental retardation( and hypogonadism; some non-typical findings could be present (cardiomyopathy, peripheral neuropathy). We report a novel homozygous mutation in the RAB3GAP1 gene in a 7-month-old boy from healthy nonconsanguineous parents from the same village in Syria, with bilateral congenital cataracts, hypogonadism, muscular hypotonia and severe developmental delay. Whole exome sequencing (WES) showed a homozygous mutation in the c.2195del p.(Pro732Glnfs*6) in exon 19 of the RAB3GAP1 gene, which is likely pathogenic and correlates with Warburg Micro syndrome type 1.

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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

Journal of Pediatric Genetics ◽

10.1055/s-0039-1700971 ◽

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.

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Whole exome sequencing identified a homozygous novel mutation in SUOX gene causes extremely rare autosomal recessive isolated sulfite oxidase deficiency and literature review

10.21203/rs.3.rs-74199/v3 ◽

2021 ◽

Author(s):

Rui Zhang ◽

Yajing Hao ◽

Ying Xu ◽

Jiale Qin ◽

Yanfang Wang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Autosomal Recessive ◽

Novel Mutation ◽

Sulfite Oxidase ◽

Loss Of Function ◽

Oxidase Deficiency ◽

Neurometabolic Disorders ◽

Whole Exome ◽

Sulfite Oxidase Deficiency

Abstract Background: Isolated sulfite oxidase deficiency (ISOD) is the rarest types of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. ISOD is extremely rare and till date only 32 mutations have been identified and reported worldwide. Germline mutation in SUOX gene causes ISOD. Methods: Here, we investigated a 5-days old Chinese female child, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, respiratory failure, cardiac failure, hyperlactatemia, severe metabolic acidosis, hyperglycemia, hyperkalemia, moderate anemia, atrioventricular block and complete right bundle branch block. Results: Whole exome sequencing identified a novel homozygous transition (c.1227G>A) in exon 6 of the SUOX gene in the proband. This novel homozygous variant leads to the formation of a truncated sulfite oxidase (p.Trp409*) of 408 amino acids. Hence, it is a loss-of-function variant. Proband’s father and mother is carrying this novel variant in a heterozygous state. This variant was not identified in 200 ethnically matched normal healthy control individuals. Conclusions: Our study not only expand the mutational spectrum of SUOX gene associated ISOD, but also strongly suggested the application of whole exome sequencing for identifying candidate genes and novel disease-causing mutations.

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Rab27a

The Journal of Cell Biology ◽

10.1083/jcb.152.4.843 ◽

2001 ◽

Vol 152 (4) ◽

pp. 843-850 ◽

Cited By ~ 157

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.

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Acitretin Treatment for Lipoid Proteinosis

Case Reports in Dermatological Medicine ◽

10.1155/2012/324506 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 2

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.

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Rapid and Easy Diagnosis of Netherton Syndrome with Dermoscopy

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2013.13106 ◽

2014 ◽

Vol 18 (4) ◽

pp. 280-282 ◽

Cited By ~ 5

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.

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Autosomal Recessive Cerebellar Ataxia type 1 mimicking multiple sclerosis: A report of two siblings with a novel mutation in SYNE1 gene in a Saudi family

Journal of the Neurological Sciences ◽

10.1016/j.jns.2016.11.036 ◽

2017 ◽

Vol 372 ◽

pp. 97-100 ◽

Cited By ~ 13

Author(s):

Hussein Algahtani ◽

Yousef Marzouk ◽

Raghad Algahtani ◽

Sali Salman ◽

Bader Shirah

Keyword(s):

Multiple Sclerosis ◽

Cerebellar Ataxia ◽

Autosomal Recessive ◽

Novel Mutation ◽

Autosomal Recessive Cerebellar Ataxia ◽

Saudi Family

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Expanding the clinical phenotype associated with NIPAL4 mutation: Study of a Tunisian consanguineous family with erythrokeratodermia variabilis—Like Autosomal Recessive Congenital Ichthyosis

PLoS ONE ◽

10.1371/journal.pone.0258777 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258777

Author(s):

Cherine Charfeddine ◽

Nadia Laroussi ◽

Rahma Mkaouar ◽

Raja Jouini ◽

Olfa Khayat ◽

...

Keyword(s):

Autosomal Recessive ◽

Mutational Analysis ◽

Clinical Phenotype ◽

Homozygous Mutation ◽

Congenital Ichthyosis ◽

Whole Exome ◽

Genes Encoding ◽

Autosomal Recessive Congenital Ichthyosis ◽

Connexin Genes ◽

Disorder Of Cornification

Erythrokeratodermia variabilis (EKV) is a rare disorder of cornification usually associated with dominant mutations in the GJB3 and GJB4 genes encoding connexins (Cx)31 and 30.3. Genetic heterogeneity of EKV has already been suggested. We investigated at the clinical and genetic level a consanguineous Tunisian family with 2 sisters presenting an autosomal recessive form of EKV to better characterize this disease. Mutational analysis initially screened the connexin genes and Whole-exome sequencing (WES) was performed to identify the molecular aetiology of the particular EKV phenotype in the proband. Migratory shaped erythematous areas are the initial presenting sign followed by relatively stable hyperkeratotic plaques are the two predominates characteristics in both patients. However, remarkable variability of morphological and dominating features of the disease were observed between patients. In particular, the younger sister (proband) exhibited ichthyosiform-like appearance suggesting Autosomal Recessive Congenital Ichthyosis (ARCI) condition. No causative mutations were detected in the GJB3 and GJB4 genes. WES results revealed a novel missense homozygous mutation in NIPAL4 gene (c.835C>G, p.Pro279Ala) in both patients. This variant is predicted to be likely pathogenic. In addition, in silico analysis of the mutated 3D domain structure predicted that this variant would result in NIPA4 protein destabilization and Mg2+ transport perturbation, pointing out the potential role of NIPAL4 gene in the development and maintenance of the barrier function of the epidermis. Taken togheter, these results expand the clinical phenotype associated with NIPAL4 mutation and reinforce our hypothesis of NIPAL4 as the main candidate gene for the EKV-like ARCI phenotype.

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

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1006351p ◽

2010 ◽

Vol 138 (5-6) ◽

pp. 351-355 ◽

Cited By ~ 1

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. .

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Case Report: A Novel PAX3 Mutation Associated With Waardenburg Syndrome Type 1

Frontiers in Genetics ◽

10.3389/fgene.2021.609040 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qiuming Hu ◽

Huazhong Ma ◽

Jiawei Shen ◽

Zongming Zhuang ◽

Jianqiang Li ◽

...

Keyword(s):

Case Report ◽

Genetic Test ◽

Novel Mutation ◽

Present Report ◽

Hereditary Disease ◽

Chinese Family ◽

Syndrome Type ◽

Waardenburg Syndrome ◽

Whole Exome

Background: Waardenburg Syndrome Type 1 (WS1) is a rare hereditary disease, which is usually caused by the mutations of PAX3 (paired box 3). Here, we reported a pedigree with WS1, which was caused by a novel mutation in PAX3.Case Report: In this present report, a 10-year-old boy and his twin sister from a Han Chinese family presented with iris pigmentary abnormality, synophrys, and broad and high nasal root. Their father presented premature whitening of the hair, but no iris pigmentary abnormality. Their aunts presented the same clinical characteristics with the twins and premature graying of hair. However, none of the patients reported hearing loss. The clinical diagnosis of the four patients from this pedigree was WS1. The whole exome sequencing (WES) revealed a novel mutation (c.959-5T>G) in the PAX3 gene, which could be responsible for the observed pathogenic of WS1 in this pedigree. The genetic test confirmed the diagnosis of WS1 in the four patients from the studied pedigree.Conclusion: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS1. The newly identified PAX3 gene mutation can expand the understanding of WS1.

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