Case of harlequin ichthyosis in preterm infant with a compound heterozygous ABCA12 missense mutation

2021 ◽  
Author(s):  
Moeka Miyazaki ◽  
Natsuki Ohkawa ◽  
Kazuki Miyabayashi ◽  
Hiromichi Shoji ◽  
Takuya Takeichi ◽  
...  
Keyword(s):  
Preterm Infant ◽  
Missense Mutation ◽  
Compound Heterozygous ◽  
Harlequin Ichthyosis

scholarly journals Compound Heterozygous Mutations Including a De Novo Missense Mutation in ABCA12 Led to a Case of Harlequin Ichthyosis with Moderate Clinical Severity

2006 ◽  
Vol 126 (7) ◽  
pp. 1518-1523 ◽  
Author(s):  
Masashi Akiyama ◽  
Kaori Sakai ◽  
Yoriko Sugiyama-Nakagiri ◽  
Yasuko Yamanaka ◽  
James R. McMillan ◽  
...  
Keyword(s):  
Missense Mutation ◽  
De Novo ◽  
Clinical Severity ◽  
Compound Heterozygous ◽  
Harlequin Ichthyosis ◽  
Compound Heterozygous Mutations

scholarly journals Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaona Luo ◽  
Chunmei Wang ◽  
Longlong Lin ◽  
Fang Yuan ◽  
Simei Wang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Neuromuscular Junctions ◽  
Three Dimensional ◽  
Missense Variant ◽  
Homozygous Deletion ◽  
Dimensional Structure ◽  
Compound Heterozygous ◽  
Splicing Mutation ◽  
Gene Encoding ◽  
Congenital Myasthenia

The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.

Novel compound heterozygous EPG5 mutations consisted with a missense mutation and a microduplication in the exon 1 region identified in a Japanese patient with Vici syndrome

2018 ◽  
Vol 176 (12) ◽  
pp. 2803-2807 ◽  
Author(s):  
Shino Shimada ◽  
Kyoko Hirasawa ◽  
Akiko Takeshita ◽  
Hidetsugu Nakatsukasa ◽  
Keiko Yamamoto-Shimojima ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Japanese Patient ◽  
Compound Heterozygous ◽  
Exon 1

scholarly journals Goitrous Congenital Hypothyroidism and Hearing Impairment Associated with Mutations in the TPO and SLC26A4/PDS Genes

2006 ◽  
Vol 91 (7) ◽  
pp. 2678-2681 ◽  
Author(s):  
Nicole Pfarr ◽  
Guntram Borck ◽  
Andrew Turk ◽  
Ulrike Napiontek ◽  
Annerose Keilmann ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Hearing Impairment ◽  
Congenital Hypothyroidism ◽  
Sensorineural Deafness ◽  
Primary Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Compound Heterozygous ◽  
Sequence Variant ◽  
Organification Defect

Abstract Context: Pendred syndrome (PS) and thyroid peroxidase (TPO) deficiency are autosomal-recessive disorders that result in thyroid dyshormonogenesis. They share congenital hypothyroidism, goiter, and an iodide organification defect as common features. Whereas the hallmark of PS is sensorineural deafness, other forms of congenital hypothyroidism may also lead to hearing impairment. Therefore, a definite diagnosis may be difficult and require molecular genetic analyses. Case Report: The propositus presented at birth with primary hypothyroidism and goiter. He also had congenital bilateral moderate hearing loss, and PS was suspected. Methods: We sequenced the SLC26A4/PDS and TPO genes in the propositus and tested familial segregation of mutations in all available family members who were phenotypically normal. The functional consequences of the identified pendrin mutation (p.R776C) were studied in vitro. Results: Sequencing of the SLC26A4/PDS gene revealed a single monoallelic missense mutation in the propositus (p.R776C). This mutation, which was inherited from his unaffected mother, has previously been identified in an individual with deafness and an enlarged vestibular aqueduct. Sequencing of the TPO gene revealed compound heterozygosity for a novel nonsense mutation (p.Q235X) and a known missense mutation (p.Y453D). The mutant pendrin (p.R776C) retained its ability to transport iodide in vitro. Conclusions: These results show that the propositus carries three sequence variants in two genes: a monoallelic SLC26A4/PDS sequence variant and compound heterozygous TPO mutations. Our study illustrates that if only a single heterozygous SLC26A4/PDS mutation is found in a patient with goiter and deafness, other genetic explanations should be considered.

scholarly journals Metabolic abnormalities in G6PC3-deficient human neutrophils result in severe functional defects

2020 ◽  
Vol 4 (23) ◽  
pp. 5888-5901
Author(s):  
Christopher McKinney ◽  
Michael Ellison ◽  
Natalie J. Briones ◽  
Angelina Baroffio ◽  
John Murphy ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Bacterial Infections ◽  
Neutrophil Function ◽  
Functional Improvement ◽  
Human Neutrophils ◽  
Compound Heterozygous ◽  
Cd11b Expression ◽  
Exon 2 ◽  
Metabolic Defects ◽  
Functional Defects

Abstract Severe congenital neutropenia type 4 (SCN-4) is an autosomal recessive condition in which mutations in the G6PC3 gene encoding for the catalytic 3 subunit of glucose-6-phosphatase-β result in neutropenia, neutrophil dysfunction, and other syndromic features. We report a child with SCN-4 caused by compound heterozygous mutations in G6PC3, a previously identified missense mutation in exon 6 (c.758G>A[p.R235H]), and a novel missense mutation in exon 2 (c.325G>A[p.G109S]). The patient had recurrent bacterial infections, inflammatory bowel disease, neutropenia, and intermittent thrombocytopenia. Administration of granulocyte colony–stimulating factor (G-CSF) resolved the neutropenia and allowed for detailed evaluation of human neutrophil function. Random and directed migration by the patient’s neutrophils was severely diminished. Associated with this were defects in CD11b expression and F-actin assembly. Bactericidal activity at bacteria/neutrophil ratios >1:1 was also diminished and was associated with attenuated ingestion. Superoxide anion generation was <25% of control values, but phox proteins appeared quantitatively normal. Extensive metabolomics analysis at steady state and upon incubation with stable isotope–labeled tracers (U-13C-glucose, 13C,15N-glutamine, and U-13C-fructose) demonstrated dramatic impairments in early glycolysis (hexose phosphate levels), hexosemonophosphate shunt (required for the generation of the NADPH), and the total adenylate pool, which could explain the dramatic cell dysfunction displayed by the patient’s neutrophils. Preliminary experiments with fructose supplementation to bypass the enzyme block demonstrated that the metabolic profile could be reversed, but was not sustained long enough for functional improvement. In human deficiency of G6PC3, metabolic defects resulting from the enzyme deficiency account for diverse neutrophil functional defects and present a major risk of infection.

scholarly journals Compound Heterozygous TGM1 Mutations Including a Novel Missense Mutation L204Q in a Mild Form of Lamellar Ichthyosis

2001 ◽  
Vol 116 (6) ◽  
pp. 992-995 ◽  
Author(s):  
Masashi Akiyama ◽  
Itsuro Matsuo ◽  
Yasuko Takizawa ◽  
Yosuke Suzuki ◽  
Akira Ishiko ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Compound Heterozygous ◽  
Mild Form ◽  
Lamellar Ichthyosis

Compound Heterozygous ABCA12 Mutations Including a Novel Nonsense Mutation Underlie Harlequin Ichthyosis

Dermatology ◽  
2007 ◽  
Vol 215 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Masashi Akiyama ◽  
Kaori Sakai ◽  
Toshihiro Sato ◽  
James R. McMillan ◽  
Maki Goto ◽  
...  
Keyword(s):  
Nonsense Mutation ◽  
Compound Heterozygous ◽  
Harlequin Ichthyosis

Identification of a novel factor X deletion in combination with a missense mutation in the F10 gene

2009 ◽  
Vol 29 (02) ◽  
pp. 184-186 ◽  
Author(s):  
J. Oldenburg ◽  
A. Pavlova ◽  
A. Superti-Furga ◽  
B. Zieger ◽  
I. Hainmann
Keyword(s):  
Missense Mutation ◽  
Young Girl ◽  
Therapeutic Options ◽  
Compound Heterozygous ◽  
Heterozygous State ◽  
Factor X ◽  
Factor X Deficiency ◽  
Relationship Of ◽  
Compound Heterozygous State

SummaryThe genotype-phenotype relationship of compound heterozygous factor X deficiency in a young girl with severe factor X deficiency and bleeding symptoms is characterized. We identified a novel deletion of exon 6 and a missense mutation (c.856G>A, Val286Met) in exon 7 of the F10 gene leading to a compound heterozygous state and causing severe factor X deficiency. Therapeutic options for patients with symptomatic factor X deficiency are demonstrated.

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