scholarly journals Report of Two Novel Mutations in Indian Patients with Rothmund–Thomson Syndrome

2019 ◽  
Vol 08 (03) ◽  
pp. 163-167
Author(s):  
Sakshi Yadav ◽  
Seema Thakur ◽  
Juergen Kohlhase ◽  
Neetu Bhari ◽  
Madhulika Kabra ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Supportive Therapy ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Skin Lesions ◽  
Poor Growth ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
Novel Variants ◽  
Rothmund Thomson Syndrome

AbstractRothmund–Thomson syndrome (RTS) is a rare autosomal recessive disorder caused by mutations in RECQL4 and has characteristic clinical features. We report two unrelated phenotypically diverse patients (cases 1 and 2) with RTS having novel variants in RECQL4 gene. Case-1 was evaluated for poor growth and recurrent fractures and skin lesions. Case-2 presented at 4 months with failure to thrive and radial ray defect and developed poikilodermatous skin lesions after infancy. Both cases were confirmed to have homozygous pathogenic variants in RECQL4. Both patients have normal intellect and are on supportive therapy. The presence of characteristic poikiloderma lesions with specific distribution and skeletal anomalies in a patient with proportionate short stature is a clue toward the diagnosis of RTS.

Molecular Analysis of the CYP11B2 Gene in 62 Patients with Hypoaldosteronism Due to Aldosterone Synthase Deficiency

2020 ◽  
Vol 106 (1) ◽  
pp. e182-e191
Author(s):  
Christina Merakou ◽  
Irene Fylaktou ◽  
Amalia Sertedaki ◽  
Maria Dracopoulou ◽  
Antonis Voutetakis ◽  
...  
Keyword(s):  
Gene Sequencing ◽  
Failure To Thrive ◽  
In Silico Analysis ◽  
Autosomal Recessive Disorder ◽  
Molecular Study ◽  
Aldosterone Synthase ◽  
Salt Wasting ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Aldosterone Synthase Deficiency

Abstract Context Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency. Objective To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency. Design Clinical and molecular study. Setting Tertiary academic Children’s Hospital, Center for Rare Pediatric Endocrine Diseases. Patients and Methods Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out to evaluate protein stability and potential pathogenicity. Results CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, 6 of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The 6 novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C, and the donor splice site variant of intron 8, c.1398 + 1G > A. Conclusion Molecular diagnosis was achieved in 62 patients with aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene.

scholarly journals Prevalent Pathogenic Variants of ATP7B in Chinese Patients with Wilson’s Disease: Geographical Distribution and Founder Effect

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 336
Author(s):  
Guo-Min Yang ◽  
Rou-Min Wang ◽  
Nan Xia ◽  
Zi-Wei Zheng ◽  
Yi Dong ◽  
...  
Keyword(s):  
Geographical Distribution ◽  
Founder Effect ◽  
Wilson’S Disease ◽  
Autosomal Recessive Disorder ◽  
Wilson's Disease ◽  
Chinese Patients ◽  
Mainland Chinese ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
The Common

Wilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the ATP7B gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (p < 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.

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.

Molecular genetic diagnostics of Bardet-Biedl syndrome with an MPS-panel

2021 ◽  
pp. 26-35
Author(s):  
М.Д. Орлова ◽  
П. Гундорова ◽  
А.В. Поляков
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Genetic Diagnostics ◽  
Bardet Biedl Syndrome ◽  
Pathogenic Variants ◽  
Development Delay ◽  
Molecular Genetic Diagnostics ◽  
First Time

Синдром Барде-Бидля - аутосомно-рецессивное заболевание, характеризующееся ожирением, пигментной дегенерацией сетчатки, полидактилией, задержкой психоречевого развития и структурными повреждениями почек. В работе представлены результаты применения МПС-панели, включающей кодирующие последовательности и прилегающие интронные области 21 гена, ассоциированного с синдромом Барде-Бидля. Впервые была проведена молекулярно-генетическая диагностика в группе из сорока российских пациентов с синдромом Барде-Бидля из неродственных семей. В результате исследования удалось подтвердить диагноз молекулярно-генетическим методом у 40% пациентов (n=16). В генах BBS1, BBS7 и BBS10 встретились повторяющиеся варианты. Частота встречаемости патогенных и вероятно патогенных вариантов в генах BBS1 и BBS10 у российских пациентов соответствует зарубежным данным. Варианты в гене BBS7 встретились у пяти человек, у четырех из них был обнаружен патогенный вариант c.1967_1968delTAinsC, не встречающийся в других популяциях. Результаты, представленные в статье, показывают значительный вклад в заболеваемость синдромом Барде-Бидля в российской популяции патогенных вариантов в гене BBS7. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney defects. This study shows the results of using an MPS panel that includes coding sequences and intronic areas of 21 genes associated with Bardet-Biedl syndrome. For the first time molecular genetic testing has been provided for the group of 40 Russian patiens with Bardet-Biedl syndrome from unrelated families. As a result of the testing, diagnoses were confirmed for 40% of the patients (n=16). The genes BBS1, BBS7, BBS10 had recurrent variants. The frequency of pathogenic and likely pathogenic variants in the genes BBS1 and BBS10 among Russian patients matches the research data in other countries. Variants in the BBS7 gene were found for five people, four of them had a pathogenic variant c.1967_1968delTAinsC, which is not present among other populations. Results provided in this article show the significant role of pathogenic variants in the BBS7 gene in patients with Bardet-Biedl syndrome in Russian population.

scholarly journals P52 Bilateral sacroiliitis in a patient with H syndrome

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Majeed Haider ◽  
Redha Ebrahim1 ◽  
Osama Alalwan
Keyword(s):  
Autosomal Recessive ◽  
Conflicts Of Interest ◽  
Autosomal Recessive Disorder ◽  
Insulin Dependent Diabetes Mellitus ◽  
Skin Lesions ◽  
Lower Limbs ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
New Feature ◽  
Slc29a3 Gene

Abstract Background Introduction H syndrome is a rare inherited form of histiocytosis. It is an autosomal recessive disorder caused by a mutation in SLC29A3 gene resulting in histiocytic infiltration of numerous organs. It becomes clinically apparent mostly during childhood with characteristic hyperpigmented hypertrichotic indurated skin lesions that mainly involve the lower limbs. Other reported features include Sensorineural hearing loss, heart anomalies, hepatosplenomegaly, lymphadenopathy, insulin dependent diabetes mellitus and flexion contractions of interphalangeal joints. We report sacroiliitis, a possible new feature, in a young girl diagnosed with H syndrome. Methods We report the case of a 16 year-old Syrian girl diagnosed to have H syndrome presented with inflammatory polyarthritis, bilateral sacroiliitis and bilateral anterior uveitis. She was managed with methotrexate and adalimumab with significant improvement. Results The findings in our patient raise the question whether she truly has a rheumatic illness beside H syndrome, or merely represent newly recognized manifestation of H syndrome. Conclusion H syndrome is a recently recognised autosomal recessive condition with characteristic dermatologic and systemic manifestation. Along with arthritis, sacroiliitis and uveitis could represent part of the phenotypic description of this rare entity. Conflicts of Interest The authors declare no conflicts of interest.

scholarly journals Prevalence of CYP17A1 gene mutations in 17α-hydroxylase deficiency in the Chinese Han population

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
Menglin Wang ◽  
Hao Wang ◽  
Haiying Zhao ◽  
Ling Li ◽  
Min Liu ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Chinese Han ◽  
Hydroxylase Deficiency ◽  
Case Presentation ◽  
Chinese Populations ◽  
Pathogenic Variants ◽  
Cytochrome P450 Family ◽  
Chinese Girls

Abstract Background 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. Case presentation In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. Conclusions All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

scholarly journals A Novel Claudinopathy Based on Claudin-10 Mutations

2019 ◽  
Vol 20 (21) ◽  
pp. 5396 ◽  
Author(s):  
Susanne Milatz
Keyword(s):  
Tight Junction ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Cation Channels ◽  
Exocrine Glands ◽  
The Past ◽  
Pathogenic Variants ◽  
Functional Relevance

Claudins are key components of the tight junction, sealing the paracellular cleft or composing size-, charge- and water-selective paracellular channels. Claudin-10 occurs in two major isoforms, claudin-10a and claudin-10b, which constitute paracellular anion or cation channels, respectively. For several years after the discovery of claudin-10, its functional relevance in men has remained elusive. Within the past two years, several studies appeared, describing patients with different pathogenic variants of the CLDN10 gene. Patients presented with dysfunction of kidney, exocrine glands and skin. This review summarizes and compares the recently published studies reporting on a novel autosomal-recessive disorder based on claudin-10 mutations.

scholarly journals Pycnodysostosis: Novel Variants in CTSK and Occurrence of Giant Cell Tumor

2017 ◽  
Vol 07 (01) ◽  
pp. 009-013 ◽  
Author(s):  
Hitesh Shah ◽  
Mohandas Nair ◽  
Krishna Sharan ◽  
Dong-Kyu Jin ◽  
Sung Cho ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Autosomal Recessive ◽  
Cathepsin K ◽  
Cell Tumor ◽  
Exon 2 ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Intron 4 ◽  
Intron 2

AbstractPycnodysostosis is an autosomal recessive skeletal dysplasia caused by pathogenic variants in the cathepsin K (CTSK) gene. We report seven patients from four unrelated families with this condition in whom we have identified three novel pathogenic variants, c.120 + 1G > T in intron 2, c.399 + 1G > A in intron 4, and c.148T > G (p.W50G) in exon 2, and a known variant, c.568C > T (p.Q190*) in exon 5 of CTSK. We present the clinical, radiographic, and molecular findings of all individuals with molecularly proven pycnodysostosis from the present cohort. We also report the occurrence of giant cell tumor in the skull of a patient with this condition.

scholarly journals Malignant infantile osteopetrosis with rickets presenting with bicytopenia in septic shock: case report

2021 ◽  
Vol 8 (7) ◽  
pp. 1268
Author(s):  
Varun Govindarajan ◽  
Thanzir Mohammed ◽  
Meghana Jagadish ◽  
Mallesh Kariyappa
Keyword(s):  
Septic Shock ◽  
Autosomal Recessive ◽  
Hematopoietic Stem Cell Transplant ◽  
Married Couple ◽  
Delayed Diagnosis ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Subarachnoid Cyst

Malignant infantile osteopetrosis is a rare, fatal autosomal recessive disorder due to abnormal osteoclast activity. We report a 1-year-old infant, born to consanguineously married couple, who presented to our ER with acute respiratory distress and bicytopenia. He had tender hepatomegaly, splenomegaly, failure to thrive and features of rickets. He was evaluated previously for possible hydrocephalus secondary to his abnormal shape of head with proptosis, MRI revealed a subarachnoid cyst, but possibility of osteopetrosis was missed. Skeletal radiographs done later detected dense, sclerotic bone with sandwich vertebra, provided a delayed diagnosis of MIOP. Rickets, a paradoxical association, was also seen in our case, with low serum calcium and vitamin D3 levels. He succumbed due to severe bronchopneumonia with septic shock. Early diagnosis and timely hematopoietic stem cell transplant are the only curative approach for MIOP, which is otherwise fatal.

scholarly journals Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

2020 ◽  
Author(s):  
Kwang Yeon Kim ◽  
Tae Hyeong Kim ◽  
Moon-Woo Seong ◽  
Sung Sup Park ◽  
Jin Soo Moon ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Total Bilirubin ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutation ◽  
University Hospital ◽  
Neonatal Cholestasis ◽  
Johnson Syndrome ◽  
Novel Variants ◽  
National University ◽  
Seoul National University

Abstract Background : Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 ( ABCC2 ). Methods: From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared. Results: A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS. Conclusions : We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.

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