Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

Watkins, Casey; Litchfield, John; Song, Eun-Kyung; Jaishankar, Gayatri Bala; Misra, Niva; Holla, Nikhil; Duffourc, Michelle M.; Krishnaswamy, Guha

doi:10.1186/1476-7961-9-13

Cited by 31 publications

(16 citation statements)

References 30 publications

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“…3,[18][19][20][21][22][23][24][25] Exact molecular diagnosis of large deletions would also add valuable information to explain symptoms associated with MLS such as X-linked CGD, retinitis pigmentosa, ornithine transcarbamylase deficiency, and DMD encoded by the respective genes CYBB, RPGR, and OTC, all located centromeric, or DMD located telomeric from Xp21.1, respectively. 26 Such diverse and large deletions are often inaccessible by utilizing "flanking" primers, with deleted (inexistent) sites to prime from.…”

Section: Resultsmentioning

confidence: 99%

Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome

et al. 2017

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BACKGROUND McLeod syndrome (MLS) is hematologically defined by the absence of the red blood cell (RBC) antigen Kx on the transmembrane RBC protein, XK, representing a highly specific diagnostic marker. Direct molecular assessment of XK therefore represents a desirable diagnostic tool. Whereas pathogenic point mutations may be simply identified, partial and complete deletions of XK on Xp21.1, eventually covering adjacent genes and causing multifaceted “continuous gene syndromes,” are difficult to localize. STUDY DESIGN AND METHODS Three different McLeod patient samples were tested using 16 initial positional polymerase chain reaction (PCR) procedures distributed over an approximately 2.8‐Mbp Xp‐chromosomal region, ranging telomeric from MAGEB16 to OTC, centromeric of XK. The molecular breakpoint of one sample with an apparent large Xp deletion was iteratively narrowed down by stepwise positioning further PCR procedures and sequenced. Two mutant XK genes, one previously published and serving as a positive control, were also sequenced. RESULTS We confirmed the positive control as previously published and listed as XK*N.20 by the International Society of Blood Transfusion (ISBT). The other XK showed a novel four‐nucleotide deletion in Exon 1, 195‐198delCCGC (newly listed as XK*N.39 by the ISBT). The third sample had an approximately 151‐kbp X‐chromosomal deletion, reaching from Exon 2 of LANCL3, across XK to Exon 3 of CYBB (newly listed as XK*N.01.016 by the ISBT). Carrier status of the patients' sister was diagnosed using a diagnostic “gap‐PCR.” CONCLUSIONS The stepwise partitioning of Xp21.1 is pragmatic and cost‐efficient in comparison to other diagnostic techniques such as “massive parallel sequencing” given the rarity of MLS. All males with suspected MLS should be considered for molecular XK profiling.

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Section: Resultsmentioning

confidence: 99%

Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome

et al. 2017

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“…One peculiar feature of this patient was that he had recurrent episodes of suppurative inflammations, which was suggestive of CGD. The X linked form of CGD is caused by mutations in the CYBB gene mapped to the Xp21.1 region 9. Large deletions that extend across multiple genes in the short arm of the X chromosome will result in ‘contiguous gene deletion syndrome’, which encompasses MLS, X linked CGD, Duchenne muscular dystrophy and X linked retinitis pigmentosa 9.…”

Section: Discussionmentioning

confidence: 99%

“…The X linked form of CGD is caused by mutations in the CYBB gene mapped to the Xp21.1 region 9. Large deletions that extend across multiple genes in the short arm of the X chromosome will result in ‘contiguous gene deletion syndrome’, which encompasses MLS, X linked CGD, Duchenne muscular dystrophy and X linked retinitis pigmentosa 9. If the elder brother was the proband who came first for clinical investigation, the most probable diagnosis would be contiguous gene deletion syndrome that involved the XK and CYBB genes.…”

Section: Discussionmentioning

confidence: 99%

The first report of a Chinese family with McLeod syndrome

Man

Yuen

2014

BMJ Case Reports

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We report the first case of a Chinese family with McLeod syndrome (MLS). The two affected brothers show significant phenotypic heterogeneity. The index case has peripheral acanthocytosis, choreoathetosis of his feet, a slowly progressive neuropathy and myopathy, and an elevated serum creatine kinase (CK) level. His elder brother has more prominent chorea of the shoulders, epilepsy, a rapidly progressive neuropathy and normal serum CK. The diagnosis of MLS was confirmed by a genetic test which showed a hemizygous frameshift mutation in theXKgene.

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“…These are missense and stop mutations anywhere in the three exons of the coding sequence as well as splice site and insertion/deletion mutations leading to erroneous translation and transcription of the gene, respectively 5 . In cases of large deletional defects, neighbour genes of XK may also be affected and give rise to the "contiguous gene syndrome" 28 , of which the clinical phenotype is dominated by the co-affected gene(s) 29 . Most important are deletions affecting DMD, a gene located telomeric to XK, leading to Duchenne muscular dystrophy 28 or deletions affecting the centromeric CYBB gene, leading to X-linked granulomatous disease (X-CGD) 30,31 .…”

Section: Peculiarity Of Blood Group Antigens On Mcleod Erythrocytesmentioning

confidence: 99%

Neurodegeneration in the elderly – When the blood type matters: An overview of the McLeod syndrome with focus on hematological features

Frey

Gassner

Jung

2015

Transfusion and Apheresis Science

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Multisystem deterioration occurs mainly in older individuals and may be related to physiological tissue degeneration. However, genetic predisposition may be unmasked by inappropriate functional and structural system deficiencies. McLeod syndrome (MLS) is a rare, multisystem disease which is X-chromosomal inherited and belongs to the neuroacanthocytosis syndromes (NAS). The main clinical manifestations contain progressive neuro-psychiatric and cognitive deterioration, choreatic movement disorder, as well as myopathy, sensory motor axonal neuropathy and cardiomyopathy. In addition, MLS patients have red blood cell abnormalities including immune-hematological, morphological and functional impairments of red blood cells. In large deletions, contiguous gene syndrome may arise, including Duchenne muscular dystrophia, cellular immunodeficiency or retinitis pigmentosa. Hematological abnormalities such as blood group abnormalities in Kell-and XK blood group system, formation of anti-public red blood cell alloantibodies, acanthocytosis and elevated creatinine phosphokinase may precede clinical disease manifestation for decades and provide tools for early diagnosis. Patients with unexplained neuro-muscular deterioration and/or neuro-psychological pathologies accompanied with hematological abnormalities should be investigated for MLS.

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Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review

Cited by 31 publications

References 30 publications

Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome

Stepwise partitioning of Xp21: a profiling method for XK deletions causative of the McLeod syndrome

The first report of a Chinese family with McLeod syndrome

Neurodegeneration in the elderly – When the blood type matters: An overview of the McLeod syndrome with focus on hematological features

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