Short-limbed dwarfism with bowing, combined immune deficiency, and late onset aplastic anaemia caused by novel mutations in the RMPR gene

Kuijpers, Taco W.

doi:10.1136/jmg.40.10.761

Cited by 35 publications

(25 citation statements)

References 43 publications

(34 reference statements)

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“…RMRP encodes the RNA component of the ribonuclease mitochondrial RNAprocessing complex, which is required for mitochondrial dNA replication. Although it is not known how defects in RMRP lead to T-cell oligoclonality and partial immunodeficiency, other mutations in RMRP cause cartilage-hair hypoplasia, a disorder that is commonly associated with partial lymphopaenia 27 and, in rare cases, with severe T-cell immunodeficiency [28][29][30] . Complete loss-of-function mutations in RMRP have not been observed.…”

Section: Autoimmune Thrombocytopaeniamentioning

confidence: 99%

Unravelling the association of partial T-cell immunodeficiency and immune dysregulation

2008

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| Partial T-cell immunodeficiencies constitute a heterogeneous cluster of disorders characterized by an incomplete reduction in T-cell number or activity. The immune deficiency component of these diseases is less severe than that of the severe T-cell immunodeficiencies and therefore some ability to respond to infectious organisms is retained. Unlike severe T-cell immunodeficiencies, however, partial immunodeficiencies are commonly associated with hyper-immune dysregulation, including autoimmunity, inflammatory diseases and elevated IgE production. This causative association is counterintuitive -immune deficiencies are caused by loss-of-function changes to the T-cell component, whereas the coincident autoimmune symptoms are the consequence of gain-offunction changes. This Review details the genetic basis of partial T -cell immunodeficiencies and draws on recent advances in mouse models to propose mechanisms by which a reduction in T-cell numbers or function may disturb the population-dependent balance between activation and tolerance.

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Section: Autoimmune Thrombocytopaeniamentioning

confidence: 99%

Unravelling the association of partial T-cell immunodeficiency and immune dysregulation

2008

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“…To date, 73 RMRP mutations have been reported (Ridanpaa et al 2001(Ridanpaa et al , 2002Bonafe et al 2002Bonafe et al , 2005Nakashima et al 2003;Kuijpers et al 2003;Harada et al 2005;Hermanns et al 2005;Thiel et al 2005). The 70A>G mutation is the most prevalent; it comprises 92% of mutations seen in the Finnish population and is commonly seen in other populations (Ridanpaa et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia

et al. 2006

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Cartilage-hair hypoplasia (CHH), or metaphyseal dysplasia, McKusick type, is an autosomal recessive disease with diverse clinical manifestations.CHH is caused by mutations in RMRP (ribonuclease mitochondrial RNA processing), the gene encoding the RNA component of the ribonucleoprotein complex RNase MRP. A common founder mutation, 70A>G has been reported in the Finnish and Amish populations. We screened 11 Japanese patients with CHH for RMRP mutations and identified mutations in five probands, including three novel mutations (16-bp dup at +1, 168G>A, and 217C>T). All patients were compound heterozygotes for an insertion or duplication in the promoter or 5¢-transcribed regions and a point mutation in the transcribed region. Two recurrent mutations were unique to the Japanese population: a 17-bp duplication at +3 and 218A>G. Haplotype analysis revealed that the two mutations common in Japanese individuals were contained within distinct haplotypes. Through this analysis, we have identified a unique mutation spectrum and founder mutations in the Japanese population.

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“…While having depressed T-cell numbers and mitogenic responses the Finnish patients appeared not to be susceptible to overwhelming viral infections and even tolerate live viral vaccines. [2][3][4][5][6][7][8][9][10][11][12][13] However, a recent review of survival in Finnish patients with CHH found increasing mortality in younger patients, suggesting that immunodeficiency was more profound than previously estimated in this population. 2 In sharp contrast, fatal varicella has been described in a few Amish patients with CHH.…”

Section: Introductionmentioning

confidence: 70%

“…19 Together, these results indicate that a small number of patients with CHH present early in life, likely in the first 2 years with profound T-cell deficiency which is indistinguishable from the presentation of SCID or Omenn syndrome. 11 The diagnosis of CHH might be delayed 9,10 if the skeletal dysplasia is not extreme as it was in patient 3. Indeed, in patient 1 and 2 the diagnosis of CHH was delayed until after failure to thrive (body weight) but not linear growth was reversed after reconstitution of the immune system with BMT.…”

Section: Discussionmentioning

confidence: 99%

“…Similar variability has been observed for the immune aberrations which are associated with CHH. While most affected individuals have mild to moderate cellular [9][10][11] or humoral 12 abnormalities, some with this syndrome present with severe combined immunodeficiency (SCID). 4,5 The immune dysfunction in the Finnish type was initially perceived to be less profound than in cases reported elsewhere.…”

Section: Introductionmentioning

confidence: 99%

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Bone marrow transplantation for cartilage-hair-hypoplasia

Guggenheim

Somech

Grunebaum

et al. 2006

Bone Marrow Transplant

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The association of cartilage hair hypoplasia (CHH) with severe combined immunodeficiency (SCID) has been known for more than three decades. Bone marrow transplantation (BMT) remains the only effective treatment that might cure SCID. Surprisingly little has been reported on the experience with BMT in CHH. We report here survival and long-term reconstitution of immunity after BMT in three patients with CHH. Regardless of whether a related human leukocyte antigen-matched or unrelated matched donors were used as the source of BMT, all patients are alive and well 5-20 years after BMT. Engraftment appears robust with most cells of donors origin. Repeated evaluation of the immune system showed normal cellular and humoral immunity. Our results should encourage the use of BMT in patients with CHH who have profound immunodeficiency.

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Short-limbed dwarfism with bowing, combined immune deficiency, and late onset aplastic anaemia caused by novel mutations in the RMPR gene

Cited by 35 publications

References 43 publications

Unravelling the association of partial T-cell immunodeficiency and immune dysregulation

Unravelling the association of partial T-cell immunodeficiency and immune dysregulation

Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia

Bone marrow transplantation for cartilage-hair-hypoplasia

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