Xq22.1 contiguous gene deletion syndrome of X-linked agammaglobulinemia and Mohr-Tranebjærg syndrome

Shaker, Marcus; Lorigiano, Ting-Jia; Vadlamudi, Anusha

doi:10.1016/j.anai.2016.03.014

Cited by 8 publications

(4 citation statements)

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“…Thus, it is important for clinicians to consider the possibility of a deletion of the last exon 19 in the BTK gene in patients suspected of having DDON syndrome, and to further test for the existence of the neighboring TIMM8A gene to allow for an effective therapeutic strategy. Applying to Italian, Chinese, American, and African cohort studies (4,12,24,25) (19,20,(26)(27)(28)(29)(30)(31)(32) including our patients P14 and P15, only one of five with a deletion of the last exon 19 in the BTK gene and the whole TIMM8A gene succumbed to pneumonitis and respiratory failure because of rapid progressive severe spasticity at 6 years of age. In contrast, the other four who had larger deletions expanding from exon 6 in the BTK gene seemed to have gradual psychomotor retardation, speech impairment, and sensorineural hearing loss.…”

Section: Discussionmentioning

confidence: 95%

“…If patients with the DDON phenotype are identified to have a deletion of exon 1 of the TIMM8A gene, the diminished BTK expression in flow cytometry and/or a B cell percentage <2% are considered to be clues to speculate whether the deletion expands to the BTK gene, thereby allowing for timely IVIG treatment. Overall, of 19 patients identified with CGS in a Medline search ( 19 , 20 , 26 – 32 ) including our patients P14 and P15, only one of five with a deletion of the last exon 19 in the BTK gene and the whole TIMM8A gene succumbed to pneumonitis and respiratory failure because of rapid progressive severe spasticity at 6 years of age. In contrast, the other four who had larger deletions expanding from exon 6 in the BTK gene seemed to have gradual psychomotor retardation, speech impairment, and sensorineural hearing loss.…”

Section: Discussionmentioning

confidence: 99%

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Distinct Clinical Features and Novel Mutations in Taiwanese Patients With X-Linked Agammaglobulinemia

et al. 2020

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Background: X-linked agammaglobulinemia (XLA) is caused by a mutation of the Bruton's tyrosine kinase (BTK) gene and is the most common genetic mutation in patients with congenital agammaglobulinemia. The aim of this study was to analyze the clinical features, genetic defects, and/or BTK expression in patients suspected of having XLA who were referred from the Taiwan Foundation of Rare Disorders (TFRD). Methods: Patients with recurrent bacterial infections in the first 2 years of life, serum IgG/A/M below 2 standard deviations of the normal range, and ≦2% CD19+B cells were enrolled during the period of 2004-2019. The frequency of infections, pathogens, B-lymphocyte subsets, and family pedigree were recorded. Peripheral blood samples were sent to our institute for BTK expression and genetic analysis. Results: Nineteen (from 16 families) out of 29 patients had BTK mutations, including 7 missense mutations, 7 splicing mutations, 1 nonsense mutation, 2 huge deletions, and 2 nucleotide deletions. Six novel mutations were detected: c.504G>T [p.K168N], c.895-2A>G [p.Del K290 fs 23 * ], c.910T>G [p.F304V], c.1132T>C [p.T334H], c.1562A>T [p.D521V], and c.1957delG [Del p.D653 fs plus 45 a.a.]. All patients with BTK mutations had obviously decreased BTK expressions. Pseudomonas sepsis developed in 14 patients and led to both Shanghai fever and recurrent hemophagocytic lymphohistiocytosis (HLH). Recurrent sinopulmonary infections and bronchiectasis occurred in 11 patients. One patient died of pseudomonas sepsis and another died of hepatocellular carcinoma before receiving optimal treatment. Two patients with contiguous gene deletion syndrome (CGS) encompassing the TIMM8A/DDP1 gene presented with early-onset progressive post-lingual sensorineural Deafness, gradual Dystonia, and Optic Neuronopathy syndrome (DDON) or Mohr-Tranebjaerg syndrome (MTS). Conclusion: Pseudomonas sepsis was more common (74%) than recurrent sinopulmonary infections in Taiwanese XLA patients, and related to Shanghai fever and Yeh et al. Unique in Taiwanese BTK Patients recurrent HLH, both of which were prevented by regular immunoglobulin infusions. Approximately 10% of patients belonged to CGS involving the TIMM8A/DDP1 gene and presented with the DDON/MTS phenotype in need of aggressive psychomotor therapy.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Distinct Clinical Features and Novel Mutations in Taiwanese Patients With X-Linked Agammaglobulinemia

et al. 2020

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“…Moreover, part of these deletions includes the closely located TIMM8A gene, and sometimes TAF7L and DRP2 genes. This type of gross deletion has been described previously only in 17 patients from 14 unrelated families [ 11 - 18 ].…”

Section: Introductionmentioning

confidence: 71%

Neurodegenerative changes detected by neuroimaging in a patient with contiguous X-chromosome deletion syndrome encompassing BTK and TIMM8A genes

Szaflarska¹,

Rutkowska-Zapała²,

Gruca³

et al. 2018

cejoi

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IntroductionIn this study we describe a patient with gross deletion containing the BTK and TIMM8A genes. Mutations in these genes are responsible for X-linked agammaglobulinemia and Mohr-Tranebjaerg syndrome, respectively. X linked agammaglobulinemia is a rare primary immunodeficiency characterized by low levels of B lymphocytes and recurrent microbial infections, whereas, Mohr-Tranebjaerg syndrome is a progressive neurodegenerative disorder with early onset of sensorineural deafness.Material and methodsFor neuroimaging, the magnetic resonance imaging and magnetic resonance spectroscopy of the brain were performed. Microarray analysis was performed to establish the extent of deletion.ResultsThe first clinical symptoms observed in our patient at the age of 6 months were connected with primary humoral immunodeficiency, whereas clinical signs of MTS emerged in the third year of live. Interestingly, the loss of speech ability was not accompanied by hearing failure. Neuroimaging of the brain suggested leukodystrophy. Molecular tests revealed contiguous X-chromosome deletion syndrome encompassing BTK (from exons 6 through 19) and TIMM8A genes. The loss of the patient’s DNA fragment was accurately localized from 100 601 727 to 100 617 576 bp on chromosome’s loci Xq22.1.ConclusionsWe diagnosed XLA-MTS in the first Polish patient on the basis of particular molecular methods. We detected neurodegenerative changes in MRI and MR spectroscopy in this patient. Our results provide further insight into this rare syndrome.

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“…3. Xq22.1 contiguous gene deletion syndrome of X-linked agammaglobulinemia associated with Mohr-Tranebjaerg syndrome (MTS) (Shaker et al 2016):…”

Section: Synonyms and Related Disordersmentioning

confidence: 99%

X-Linked Agammaglobulinemia

Chen¹

2016

Atlas of Genetic Diagnosis and Counseling

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Xq22.1 contiguous gene deletion syndrome of X-linked agammaglobulinemia and Mohr-Tranebjærg syndrome

Cited by 8 publications

References 9 publications

Distinct Clinical Features and Novel Mutations in Taiwanese Patients With X-Linked Agammaglobulinemia

Distinct Clinical Features and Novel Mutations in Taiwanese Patients With X-Linked Agammaglobulinemia

Neurodegenerative changes detected by neuroimaging in a patient with contiguous X-chromosome deletion syndrome encompassing BTK and TIMM8A genes

X-Linked Agammaglobulinemia

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