Novel ABCD1 Gene Mutation in Adrenomyeloneuropathy with Hypoplasia and Agenesis of the Corpus Callosum

2018 ◽  
Vol 18 (2-3) ◽  
pp. 156-164 ◽  
Author(s):  
Yusen Qiu ◽  
Ling Xin ◽  
Yuyao Wang ◽  
Yanyan Yu ◽  
Keji Zou ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Exome Sequencing ◽  
Gene Mutation ◽  
Whole Exome Sequencing ◽  
Index Case ◽  
Spastic Paraparesis ◽  
Clinical Manifestations ◽  
Whole Exome ◽  
Cerebral Mri ◽  
Abcd1 Gene

Background: Adult adrenomyeloneuropathy (AMN) is caused by mutations in the ABCD1 gene. Some pure AMN patients develop cerebral demyelination late in life. However, hypoplasia and agenesis of the corpus callosum (CC) has never been reported in AMN patients. Objective: To describe a new clinical variant of AMN that is possibly caused by a novel ABCD1 gene mutation. Methods: A total of 10 members in an X-linked inherited family were examined. The age at onset, progression of disability, and clinical manifestations were collected. Blood tests of the index case were conducted in an academic hospital. Cerebral and spinal MRI was performed in 4 affected members using a Siemens 3.0-T or Hitachi 1.0-T MR scanner. Whole-exome sequencing was conducted in the index case, which was subsequently validated by Sanger sequencing in the family. Results: The patients displayed typical degenerative spastic paraparesis and peripheral sensorimotor neuropathy with some intrafamilial variations. In addition to neurological deficits, all male patients displayed alopecia since adolescence. Furthermore, an increase in plasma long-chain fatty acids was observed. Based on these presentations, adult AMN was diagnosed for the patients. Intriguingly, cerebral MRI showed multiple types of hypoplasia and agenesis of the CC including anterior remnant CC agenesis, truncated corpus and splenium, anterior remnant CC agenesis along with thin corpus and splenium. Whole-exome sequencing revealed a nonsense mutation (c.231G>A) which results in a truncated protein product (p.W77X) that might be nonfunctional. No other mutations associated with alopecia or hypoplasia and agenesis of the CC were identified in the exome-sequencing database. Conclusion: In addition to the typical symptoms such as spastic myelopathy, cognitive impairment, mixed neuropathy, and alopecia, AMN patients can also display hypoplasia and agenesis of the CC, which was not described in the other AMN patients reported before.

scholarly journals Facial cleft? The first case of manitoba‐oculo‐tricho‐anal syndrome with novel mutations in China: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuchen Gu ◽  
Yimin Khoong ◽  
Xin Huang ◽  
Tao Zan
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Manifestations ◽  
Sporadic Case ◽  
Facial Cleft ◽  
Ocular Manifestations ◽  
First Case ◽  
Whole Exome ◽  
Chinese Girl ◽  
Low Prevalence

Abstract Background Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare syndrome with only 27 cases reported worldwide so far, but none was reported in the population of Eastern Asia. Such extremely low prevalence might be contributed by misdiagnosis due to its similarities in ocular manifestations with facial cleft. In our study, we discovered the first case of MOTA syndrome in the population of China, with 2 novel FRAS1 related extracellular matrix 1 (FREM1) gene stop-gain mutations confirmed by whole exome sequencing. Case presentation A 12-year-old Chinese girl presented with facial cleft-like deformities including aberrant hairline, blepharon-coloboma and broad bifid nose since birth. Whole exome sequencing resulted in the identification of 2 novel stop-gain mutations in the FREM1 gene. Diagnosis of MOTA syndrome was then established. Conclusions We discovered the first sporadic case of MOTA syndrome according to clinical manifestations and genetic etiology in the Chinese population. We have identified 2 novel stop-gain mutations in FREM1 gene which further expands the spectrum of mutational seen in the MOTA syndrome. Further research should be conducted for better understanding of its mechanism, establishment of an accurate diagnosis, and eventually the exploitation of a more effective and comprehensive therapeutic intervention for MOTA syndrome.

scholarly journals Whole-Exome Sequencing Identifies Mutated C12orf57 in Recessive Corpus Callosum Hypoplasia

2013 ◽  
Vol 92 (3) ◽  
pp. 392-400 ◽  
Author(s):  
Naiara Akizu ◽  
Nuri M. Shembesh ◽  
Tawfeg Ben-Omran ◽  
Laila Bastaki ◽  
Asma Al-Tawari ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome

scholarly journals Defining Clonal Plasticity Using Whole Exome Sequencing in Single Cells in an Index Case of amp1q21 Multiple Myeloma

2017 ◽  
Vol 17 (1) ◽  
pp. e108
Author(s):  
Surinder Sahota ◽  
Dean Bryant ◽  
Nicola Weston-Bell ◽  
Will Tapper ◽  
Arnold Bolomsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Index Case ◽  
Single Cells ◽  
Whole Exome

Gene mutation screening using whole exome sequencing in lipid storage myopathy

2015 ◽  
Vol 25 ◽  
pp. S204
Author(s):  
K. Takayama ◽  
S. Mitsuhashi ◽  
I. Nonaka ◽  
S. Noguchi ◽  
I. Nishino
Keyword(s):  
Exome Sequencing ◽  
Gene Mutation ◽  
Whole Exome Sequencing ◽  
Mutation Screening ◽  
Lipid Storage ◽  
Lipid Storage Myopathy ◽  
Whole Exome

scholarly journals Phenotypic Heterogeneity and Genotypic Spectrum of Primary Immunodeficiencies with Whole Exome Sequencing in a Thai Patient Cohort

2021 ◽  
Author(s):  
Maliwan Tengsujaritkul ◽  
Narissara Suratannon ◽  
Chupong Ittiwut ◽  
Rungnapa Ittiwut ◽  
Pantipa Chatchatee ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Decision Making ◽  
Diagnostic Yield ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Genetic Defects ◽  
Diagnostic Strategy ◽  
Patient Cohort ◽  
Whole Exome

Background: Primary immunodeficiency diseases (PIDs) comprise more than 400 rare diseases with potential life-threatening conditions. Clinical manifestations and genetic defects are heterogeneous and diverse among populations. Here, we aimed to characterize the clinical, immunological and genetic features of Thai pediatric patients with PIDs. The use of whole exome sequencing (WES) in diagnosis and clinical decision making was also assessed. Methods: 36 unrelated patients with clinical and laboratory findings consistent with PIDs were recruited from January 2010 to December 2020. WES was performed to identify the underlying genetic defects. Results: The median age of disease onset was 4 months (range; 1 month to 13 years) and 24 were male (66.7%). Recurrent sinopulmonary tract infection was the most common clinical presentation followed by septicemia, and severe pneumonia. Using WES, we successfully identified the underlying genetic defects in 18 patients (50%). Of the 20 variants identified, six have not been previously described (30%). According to the International Union of Immunological Societies (IUIS), 38.9% of these detected cases (7/18) were found to harbor variants associated with genes in combined immunodeficiencies with associated or syndromic features (Class II). Conclusion: The diagnostic yield of WES in this patient cohort was 50%. Six novel genetic variants in PID genes were identified. The clinical usefulness of WES in PIDs was demonstrated, emphasizing it as an effective diagnostic strategy in these genetically heterogeneous disorders.

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