scholarly journals Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy

2003 ◽  
Vol 88 (10) ◽  
pp. 4840-4847 ◽  
Author(s):  
Anil K. Agarwal ◽  
Vinaya Simha ◽  
Elif Arioglu Oral ◽  
Stephanie A. Moran ◽  
Phillip Gorden ◽  
...  
Keyword(s):  
Genetic Heterogeneity ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Limited Data ◽  
Lower Serum ◽  
Phenotypic Differences ◽  
Congenital Generalized Lipodystrophy ◽  
High Prevalence ◽  
Novel Variants ◽  
Onset Of Diabetes

Abstract Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.

scholarly journals McArdle disease and pregnancy: A case report and scoping review of pregnancy outcomes

2021 ◽  
pp. 1753495X2110161
Author(s):  
Christopher M Nash ◽  
Nabha Shetty ◽  
Ashley Miller ◽  
Kyle McCoy
Keyword(s):  
Scoping Review ◽  
Pregnancy Outcomes ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Glycogen Metabolism ◽  
Limited Data ◽  
Genetic Condition ◽  
Second Stage ◽  
Mcardle Disease ◽  
Pregnancy And Delivery

McArdle disease is an autosomal recessive disorder affecting skeletal muscle glycogen metabolism. Limited data are available regarding pregnancy outcomes with this genetic condition. We present a recent case of a woman with McArdle disease, along with a scoping review of all published literature regarding pregnancy and delivery outcomes for women with McArdle disease. A total of 35 cases are summarised. Overall, pregnancy does not worsen or increase the risk for disease flare. Women can successfully deliver vaginally, with consideration of an assisted second stage recommended to reduce the risk of postpartum rhabdomyolysis.

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.

Hypomagnesemia with Secondary Hypoparathyroidism and Hypocalcemia due to Novel Variants in the Transient Receptor Potential Cation Channel Subfamily M Member 6 (TRPM6) Gene

2021 ◽  
Author(s):  
Geetanjali Jain ◽  
Gourab Das ◽  
Rakhi Malhotra ◽  
Sateesh Ramchandran ◽  
Nagaraja M. Phani ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Autosomal Recessive Disorder ◽  
Cation Channel ◽  
Neonatal Seizures ◽  
Rare Autosomal Recessive Disorder ◽  
Novel Variants ◽  
Transient Receptor ◽  
Trpm6 Gene

AbstractHOMG1 (hypomagnesemia 1, intestinal) or hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder of magnesium metabolism, characterized by impaired magnesium absorption. This disorder may mimic other conditions presenting with neonatal seizures. Here, we report an infant diagnosed to have hypomagnesemia with secondary hypocalcemia due to novel variants in TRPM6 gene.

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.

Mutations in Fucosidosis Gene: a Review

1995 ◽  
Vol 44 (3-4) ◽  
pp. 223-232 ◽  
Author(s):  
G. Tiberio ◽  
M. Filocamo ◽  
R. Gatti ◽  
P. Durand
Keyword(s):  
Ethnic Groups ◽  
Genetic Heterogeneity ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Phenotype Correlation ◽  
Clinical Variability ◽  
Genotype Phenotype Correlation

AbstractFucosidosis is an autosomal recessive disorder caused by a deficiency of alpha-L-fucosidase. Up to now 79 cases have been described and several others identified but not yet published. The higher incidence of the disease is in Italy, where nearly 20 patients have been identified. Fourteen disease-causing mutations have been detected and four of them, Q422X, G60D, E375X, P141fs are present in more than 70% of the forty patients studied. In Italian patients, only seven mutations have been described and P141fs and G60D mutations are present in more than 50% of the cases. The P141fs mutation is absent in other ethnic groups. It has been impossible to establish genotype-phenotype correlation so far and the clinical variability of the disease cannot be explained only by genetic heterogeneity.

scholarly journals Identification of Novel and Recurrent Variants in MYO15A in Ashkenazi Jewish Patients With Autosomal Recessive Nonsyndromic Hearing Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Kevin T. Booth ◽  
Yoel Hirsch ◽  
Anna C. Vardaro ◽  
Josef Ekstein ◽  
Devorah Yefet ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Null Allele ◽  
Mutation Screening ◽  
Ashkenazi Jewish ◽  
Locus Heterogeneity ◽  
Phenotypic Differences ◽  
Ashkenazi Jewish Population ◽  
Targeted Mutation ◽  
Novel Variants

Hearing loss is a genetically and phenotypically heterogeneous disorder. The purpose of this study was to determine the genetic cause underlying hearing loss in four Ashkenazi Jewish families. We screened probands from each family using a combination of targeted mutation screening and exome sequencing to identifiy the genetic cause of hearing loss in each family. We identified four variants in MYO15A, two novel variants never previously linked to deafness (c.7212+5G>A and p.Leu2532ArgfsTer37) and two recurrent variants (p.Tyr2684His and p.Gly3287Gly). One family showed locus heterogeneity, segregrating two genetic forms of hearing loss. Mini-gene assays revealed the c.7212+5G>A variant results in abnormal splicing and is most likely a null allele. We show that families segregrating the p.Gly3287Gly variant show both inter and intra-familial phenotypic differences. These results add to the list of MYO15A deafness-causing variants, further confirm the pathogenicity of the p.Gly3287Gly variant and shed further light on the genetic etiology of hearing loss in the Ashkenazi Jewish population.

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):  
Genetic Analysis ◽  
Autosomal Recessive ◽  
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. Genetic analysis was performed by neonatal cholestasis gene panel. 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.

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):  
Genetic Analysis ◽  
Autosomal Recessive ◽  
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. Genetic analysis was performed by neonatal cholestasis gene panel. 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.

scholarly journals Novel CUL7 biallelic mutations alter the skeletal phenotype of 3M syndrome

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nao Takizaki ◽  
Yoshinori Tsurusaki ◽  
Kaoru Katsumata ◽  
Yumi Enomoto ◽  
Hiroaki Murakami ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Neonatal Period ◽  
Autosomal Recessive Disorder ◽  
Facial Features ◽  
Skeletal Changes ◽  
Novel Variants ◽  
Skeletal Phenotype ◽  
Vertebral Bodies ◽  
Biallelic Mutations ◽  
Severe Growth

Abstract3M syndrome is an autosomal recessive disorder characterized by severe growth retardation, distinct facial features, and skeletal changes, including long slender tubular bones and tall vertebral bodies. We report a Japanese patient with 3M syndrome caused by the biallelic novel variants c.1705_1708del and c.1989_1999del of CUL7. Skeletal features were consistent with 3M syndrome in the early neonatal period but became less obvious by 2 years of age.

High prevalence of non-HFE gene-associated haemochromatosis in patients from southern Italy

2004 ◽  
Vol 42 (1) ◽  
Author(s):  
F. De Marco ◽  
R. Liguori ◽  
M. G. Giardina ◽  
M. D'Armiento ◽  
E. Angelucci ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Southern Italy ◽  
Single Point ◽  
Point Mutations ◽  
Autosomal Recessive Disorder ◽  
Iron Regulation ◽  
Hfe Gene ◽  
High Prevalence ◽  
Single Point Mutations ◽  
Parenchymal Cells

AbstractHereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the

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