Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific <i>HAX1</i> mutations

Carlsson, Göran; Hooft, Ingrid van’t; Melin, Malin; Entesarian, Miriam; Laurenčikas, Evaldas; Nennesmo, Inger; Trębińska, Alicja; Grzybowska, Ewa A.; Palmblad, Jan; Dahl, Niklas; Nordenskjöld, Magnus; Fadeel, Bengt; Henter, Jan‐Inge

doi:10.1111/j.1365-2796.2008.01982.x

Cited by 76 publications

(111 citation statements)

References 36 publications

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“…[4][5][6] A correlation between genotype and phenotype was observed in these patients, suggesting that mutations affecting transcript variant 1 of HAX1 were associated with CN alone, whereas mutations affecting both transcripts caused CN and neurological symptoms. [6][7][8] This finding implies isoform b of the HAX1 protein is critical for neuronal function, which has also been confirmed in an animal experiment. 9 The present study describes the first Chinese autosomal recessive SCN patient with chronic myelomonocytic leukemia (CMML) transformation, who carries a novel compound heterozygous mutation in the HAX1 gene that affects both transcripts without neurodevelopmental abnormalities.…”

supporting

confidence: 61%

A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities

Xue¹,

Li²,

Zou³

et al. 2011

Haematologica

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supporting

confidence: 61%

A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities

Xue¹,

Li²,

Zou³

et al. 2011

Haematologica

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“…The patients both harbor inherited mutations in the HAX1 gene known to be an underlying cause of autosomal recessive SCN (14). Detailed clinical descriptions of these patients were recently reported (15). Patient 1 thus belongs to the original Kostmann family in northern Sweden and carries the "classical" homozygous HAX1 mutation identified in this kindred (568C3 T, Q190X), whereas patient 2 harbors an alternative homozygous HAX1 mutation (131G3 A, W44X).…”

Section: Generation and In Vitro Culture Of Human B Cell Lines-thementioning

confidence: 97%

Nα-Tosyl-l-phenylalanine Chloromethyl Ketone Induces Caspase-dependent Apoptosis in Transformed Human B Cell Lines with Transcriptional Down-regulation of Anti-apoptotic HS1-associated Protein X-1

Jitkaew

Trębińska

Grzybowska

et al. 2009

Journal of Biological Chemistry

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was originally synthesized as a specific inhibitor of chymotrypsin-like serine proteases (1) and has been widely used to investigate signal transduction pathways that are involved in gene expression and cell survival/cell death. However, contradictory effects of TPCK on apoptosis have been reported. Hence, TPCK was shown to prevent apoptosis in a cell death stimulus-dependent manner in some model systems (2-4), and a recent study also suggested that TPCK may diminish apoptosis by direct and nonspecific inhibition of active caspases (5). On the other hand, TPCK was also reported to potentiate apoptosis induced by certain apoptotic stimuli, and this was suggested to occur, at least in some cases, through activation of cell cycle checkpoints via inhibition of the proteasome (3, 6). TPCK alone may also induce apoptosis. TPCK thus caused a reduction in activity of the transcription factor, NF-B, in a murine B lymphoma cell line resulting in a decrease in c-myc and activation of apoptosis (7,8). Subsequent studies have shown that TPCK can induce apoptosis in a human acute monocytic leukemia cell line through activation of mitochondria-dependent apoptosis signaling (4, 9). Studies in transformed human T cells also indicated that TPCK can induce apoptosis through inhibition of constitutive NF-B activation, and it was proposed that TPCK might affect sulfhydryl groups on proteins involved in regulating cell survival and NF-B acti- 4 The abbreviations used are: TPCK, N ␣ -tosyl-L-phenylalanine chloromethyl ketone; z, N-benzyloxycarbonyl; fmk, fluoromethyl ketone; AIF, apoptosisinducing factor; cIAP1, cellular inhibitor of apoptosis protein-1; cIAP2, cellular inhibitor of apoptosis protein-2; AMC, 7-amino-4-methylcoumarin; DHE, dihydroethidium; ⌬ m , mitochondrial transmembrane potential; EBV, Epstein-Barr virus; HAX-1, HS1-associated protein X-1; IB, inhibitor of NF-B; NAC, N-acetylcysteine; NF-B, nuclear factor B; PARP, poly(ADPribose) polymerase; PI, propidium iodide; ROS, reactive oxygen species; SCN, severe congenital neutropenia; TMRE, tetramethylrhodamine ethyl ester; XIAP, X chromosome-linked inhibitor of apoptosis protein.

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“…The severe neutropenia is often associated with neurologic and neurocognitive deficits, particulary if the mutation affects both HAX-1 isoforms (33).…”

Section: Mechanisms Of Inherited Neutropeniamentioning

confidence: 99%

Cellular stress pathways in pediatric bone marrow failure syndromes: many roads lead to neutropenia

2013

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Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations

Cited by 76 publications

References 36 publications

A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities

A novel compound heterozygous HAX1 mutation in a Chinese patient with severe congenital neutropenia and chronic myelomonocytic leukemia transformation but without neurodevelopmental abnormalities

Nα-Tosyl-l-phenylalanine Chloromethyl Ketone Induces Caspase-dependent Apoptosis in Transformed Human B Cell Lines with Transcriptional Down-regulation of Anti-apoptotic HS1-associated Protein X-1

Cellular stress pathways in pediatric bone marrow failure syndromes: many roads lead to neutropenia

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