-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Gibbons, Richard J.

doi:10.1101/cshperspect.a011759

Cited by 33 publications

(27 citation statements)

References 58 publications

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“…Although the clinical penetrance is quite variable in the most common forms of hereditary hemochromatosis, communal iron fortification for this group is generally not recommended. Another genetic disorder named thalassemia (see Fucharoen and Weatherall 2012; Gibbons 2012; Musallam et al 2012; Nienhuis and Nathan 2012; Cao and Kan 2013; Higgs 2013; Thein 2013; Vichinsky 2013) has a more direct relationship with iron deficiency anemia, because both diseases are concentrated within malaria and hookworm-endemic regions of the world. Thalassemia is caused by mutations in the globin genes that lead to decreased production of hemoglobin.…”

Section: Solving the Global Problemmentioning

confidence: 99%

Iron Deficiency Anemia: A Common and Curable Disease

Miller

2013

Cold Spring Harbor Perspectives in Medicine

439

309

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Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body’s loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations.

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Section: Solving the Global Problemmentioning

confidence: 99%

Iron Deficiency Anemia: A Common and Curable Disease

Miller

2013

Cold Spring Harbor Perspectives in Medicine

439

309

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“…Similarly, hemoglobin H inclusions can be seen on blood smear in some affected individuals, but these inclusions may be visible in only a small proportion (less than 1%) of the erythrocytes or completely absent in other affected individuals. Carrier females with highly skewed X‐inactivation patterns appear to be asymptomatic [Stevenson, ; Gibbons, ].…”

Section: Single Gene Syndromesmentioning

confidence: 99%

If not Angelman, what is it? a review of Angelman‐like syndromes

Tan

Bird

Thibert

et al. 2014

American J of Med Genetics Pt A

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Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan–McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt–Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat–Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes.

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“…Until now, 11 cases due to deletions, between 900 and 1,700 kb that lead to pure monosomy of 16p13.3 have been reported. The affected patients present heterogeneous clinical signs: various developmental abnormalities (e.g., skeletal abnormalities and facial dysmorphisms: most commonly featuring a high forehead, mild hypertelorism, and a broad or prominent nasal bridge) and mild intellectual disability [Gibbons, ; Higgs, ; Weatherall, ]. Currently, the mechanism responsible for the observed phenotypes has not been identified: it was proposed that certain affected gene/s could be subjected to imprinting, although no conclusive evidence was obtained to support this.…”

Section: Introductionmentioning

confidence: 99%

Multiple copy number variants in a pediatric patient with Hb H disease and intellectual disability

Scheps

Francipane

Nevado

et al. 2016

American J of Med Genetics Pt A

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Two distinct syndromes that link α-thalassemia and intellectual disability (ID) have been described: ATR-X, due to mutations in the ATRX gene, and ATR-16, a contiguous gene deletion syndrome in the telomeric region of the short arm of chromosome 16. A critical region where the candidate genes for the ID map has been established. In a pediatric patient with Hemoglobin H disease, dysmorphic features and ID, 4 novel and clinically relevant Copy Number Variants were identified. PCR-GAP, MLPA and FISH analyses established the cause of the α-thalassemia. SNP-array analysis revealed the presence of 4 altered loci: 3 deletions (arr[hg19]Chr16(16p13.3; 88,165-1,507,988) x1; arr[hg19]Chr6(6p21.1; 44,798,701-45,334,537) x1 and arr[hg19]Chr17(17q25.3; 80,544,855-81,057,996) x1) and a terminal duplication (arr[hg19]Chr7(7p22.3-p22.2; 4,935-4,139,785) x3). The -α(3.7) mutation and the ∼1.51 Mb in 16p13.3 are involved in the alpha-thalassemic phenotype. However, the critical region for ATR-16 cannot be narrowed down. The deletion affecting 6p21.1 removes the first 2 exons and part of intron 2 of the RUNX2 gene. Although heterozygous loss of function mutations affecting this gene have been associated with cleidocranial dysplasia, the patient does not exhibit pathognomonic signs of this syndrome, possibly due to the fact that the isoform d of the transcription factor remains unaffected. This work highlights the importance of searching for cryptic deletions in patients with ID and reiterates the need of the molecular analysis when it is associated to microcytic hypochromic anemia with normal iron status.

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-Thalassemia, Mental Retardation, and Myelodysplastic Syndrome

Cited by 33 publications

References 58 publications

Iron Deficiency Anemia: A Common and Curable Disease

Iron Deficiency Anemia: A Common and Curable Disease

If not Angelman, what is it? a review of Angelman‐like syndromes

Multiple copy number variants in a pediatric patient with Hb H disease and intellectual disability

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