scholarly journals A case of sitosterolemia due to compound heterozygous mutations in ABCG5: clinical features and treatment outcomes obtained with colestimide and ezetimibe

2017 ◽  
Vol 26 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Sahoko Ono ◽  
Junko Matsuda ◽  
Aki Saito ◽  
Takenobu Yamamoto ◽  
Wataru Fujimoto ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Clinical Features ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

Distal arthrogryposis type 5D with novel clinical features and compound heterozygous mutations in ECEL1

2014 ◽  
Vol 164 (7) ◽  
pp. 1846-1849 ◽  
Author(s):  
Christopher P. Barnett ◽  
Emily J. Todd ◽  
Royston Ong ◽  
Mark R. Davis ◽  
Vanessa Atkinson ◽  
...  
Keyword(s):  
Clinical Features ◽  
Compound Heterozygous ◽  
Distal Arthrogryposis ◽  
Compound Heterozygous Mutations

Primary Microcephaly With Anterior Predominant Pachygyria Caused by Novel Compound Heterozygous Mutations in ASPM

2015 ◽  
Vol 52 (5) ◽  
pp. e7-e8 ◽  
Author(s):  
Kazuyuki Nakamura ◽  
Takehiko Inui ◽  
Fuyuki Miya ◽  
Yonehiro Kanemura ◽  
Nobuhiko Okamoto ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Primary Microcephaly ◽  
Compound Heterozygous Mutations

Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia

2021 ◽  
Author(s):  
Yamato Ishida ◽  
Takuya Kobayashi ◽  
Shuhei Chiba ◽  
Yohei Katoh ◽  
Kazuhisa Nakayama
Keyword(s):  
Protein Trafficking ◽  
Primary Cilia ◽  
Intraflagellar Transport ◽  
Missense Variant ◽  
Cellular Level ◽  
Compound Heterozygous ◽  
Hypomorphic Allele ◽  
Genes Encoding ◽  
Specific Proteins ◽  
Compound Heterozygous Mutations

Abstract Primary cilia contain specific proteins to achieve their functions as cellular antennae. Ciliary protein trafficking is mediated by the intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes. Mutations in genes encoding the IFT-A subunits (IFT43, IFT121/WDR35, IFT122, IFT139/TTC21B, IFT140, and IFT144/WDR19) often result in skeletal ciliopathies, including cranioectodermal dysplasia (CED). We here characterized the molecular and cellular defects of CED caused by compound heterozygous mutations in IFT144 [the missense variant IFT144(L710S) and the nonsense variant IFT144(R1103*)]. These two variants were distinct with regard to their interactions with other IFT-A subunits and with the IFT-B complex. When exogenously expressed in IFT144-knockout (KO) cells, IFT144(L710S) as well as IFT144(WT) rescued both moderately compromised ciliogenesis and the abnormal localization of ciliary proteins. As the homozygous IFT144(L710S) mutation was found to cause autosomal recessive retinitis pigmentosa, IFT144(L710S) is likely to be hypomorphic at the cellular level. In striking contrast, the exogenous expression of IFT144(R1103*) in IFT144-KO cells exacerbated the ciliogenesis defects. The expression of IFT144(R1103*) together with IFT144(WT) restored the abnormal phenotypes of IFT144-KO cells. However, the coexpression of IFT144(R1103*) with the hypomorphic IFT144(L710S) variant in IFT144-KO cells, which mimics the genotype of compound heterozygous CED patients, resulted in severe ciliogenesis defects. Taken together, these observations demonstrate that compound heterozygous mutations in IFT144 cause severe ciliary defects via a complicated mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.

Afibrinogenemia with two compound heterozygous mutations in FGA gene

Haemophilia ◽  
2021 ◽  
Author(s):  
Guillaume Feugray ◽  
Paul Billoir ◽  
Alessandro Casini ◽  
M. Neerman‐Arbez ◽  
Virginie Barbay ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

2020 ◽  
Vol 33 (5) ◽  
pp. 671-674
Author(s):  
Tashunka Taylor-Miller ◽  
Jayne Houghton ◽  
Paul Munyard ◽  
Yadlapalli Kumar ◽  
Clinda Puvirajasinghe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Newborn Period ◽  
Case Presentation ◽  
Male Baby ◽  
Common Causes ◽  
Compound Heterozygous Mutations

AbstractBackgroundCongenital hyperinsulinism (CHI), a condition characterized by dysregulation of insulin secretion from the pancreatic β cells, remains one of the most common causes of hyperinsulinemic, hypoketotic hypoglycemia in the newborn period. Mutations in ABCC8 and KCNJ11 constitute the majority of genetic forms of CHI.Case presentationA term macrosomic male baby, birth weight 4.81 kg, born to non-consanguineous parents, presented on day 1 of life with severe and persistent hypoglycemia. The biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and progressively increased to 15 mg/kg/day to maintain normoglycemia. Sequence analysis identified compound heterozygous mutations in ABCC8 c.4076C>T and c.4119+1G>A inherited from the unaffected father and mother, respectively. The mutations are reported pathogenic. The patient is currently 7 months old with a sustained response to diazoxide.ConclusionsBiallelic ABCC8 mutations are known to result in severe, diffuse, diazoxide-unresponsive hypoglycemia. We report a rare patient with CHI due to compound heterozygous mutations in ABCC8 responsive to diazoxide.

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