Limb defects and congenital anomalies of the genitalia in an infant with homozygous α-thalassemia

Abuelo, Dianne; Forman, Edwin N.; Rubin, Lewis P.

doi:10.1002/(sici)1096-8628(19970120)68:2<158::aid-ajmg7>3.0.co;2-l

Cited by 41 publications

(25 citation statements)

References 17 publications

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“…Syndactyly associated with a decrease in embryonic oxygen supply is observed in congenital anemias, i.e. homozygous α-thalassemia, congenital dyserythropoietic anemia type I and Fanconi anemia (Abuelo et al, 1997;Adam et al, 2005;Brichard et al, 1994;Sadler and Rasmussen, 2010).…”

Section: Discussionmentioning

confidence: 99%

Vascular patterning regulates interdigital cell death by a ROS-mediated mechanism

Eshkar-Oren

Krief

Ferrara³

et al. 2015

Development

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Blood vessels serve as key regulators of organogenesis by providing oxygen, nutrients and molecular signals. During limb development, programmed cell death (PCD) contributes to separation of the digits. Interestingly, prior to the onset of PCD, the autopod vasculature undergoes extensive patterning that results in high interdigital vascularity. Here, we show that in mice, the limb vasculature positively regulates interdigital PCD. In vivo, reduction in interdigital vessel number inhibited PCD, resulting in syndactyly, whereas an increment in vessel number and distribution resulted in elevation and expansion of PCD. Production of reactive oxygen species (ROS), toxic compounds that have been implicated in PCD, also depended on interdigital vascular patterning. Finally, ex vivo incubation of limbs in gradually decreasing oxygen levels led to a correlated reduction in both ROS production and interdigital PCD. The results support a role for oxygen in these processes and provide a mechanistic explanation for the counterintuitive positive role of the vasculature in PCD. In conclusion, we suggest a new role for vascular patterning during limb development in regulating interdigital PCD by ROS production. More broadly, we propose a double safety mechanism that restricts PCD to interdigital areas, as the genetic program of PCD provides the first layer and vascular patterning serves as the second.

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Section: Discussionmentioning

confidence: 99%

Vascular patterning regulates interdigital cell death by a ROS-mediated mechanism

Eshkar-Oren

Krief

Ferrara³

et al. 2015

Development

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“…And despite the relative genetic uniformity of Hb Barts Hydrops fetalis syndrome there is considerable phenotypic variation. For example, associated developmental abnormalities have been reported in up to 17 % of cases and there is considerable variation in the pace and extent of abnormal development in fetal life [41]. Although these observations have been explained as being the result of variation in the severity of intra-uterine anaemia, this is difficult to prove and may not be the whole story [5].…”

Section: Phenotype/genotype Relationshipsmentioning

confidence: 99%

The Alpha Thalassaemias

Higgs

Weatherall

2008

Cell. Mol. Life Sci.

118

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Recent work in the alpha thalassaemia field has started to provide some indication of the mechanisms involved in the very high frequency of the different forms of alpha thalassaemia among the populations of tropical countries, and, at the same time, is starting to define at least some of the mechanisms for its remarkable phenotypic heterogeneity. These diseases continue to provide extremely valuable models for the better understanding of the regulation of the alpha globin genes, and for human molecular pathology in general. The much less common disorders, ATR-16 and ATR-X are also providing valuable information about the spectrum of molecular lesions associated with different forms of mental retardation and about the molecular mechanisms involved in their varying phenotypes.

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“…D'autres anomalies sont décrites : hydrocéphalie, microcéphalie, anomalies cardiopulmonaires, des anomalies urogénitales et des anomalies squelettiques et des extré-mités dont l'origine de rupture vasculaire précoce a été évoquée [5,6]. L'anasarque foetoplacentaire est souvent associée, elle est la conséquence d'une insuffisance cardiaque liée à l'anémie.…”

Section: Discussionunclassified

Alpha-thalassémie majeure : à propos d’un cas de dépistage anténatal et revue de la littérature

Saadi

Alexander

Barlow

et al. 2009

Journal de Gynécologie Obstétrique et Biologie de la Reproducti

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Limb defects and congenital anomalies of the genitalia in an infant with homozygous α-thalassemia

Cited by 41 publications

References 17 publications

Vascular patterning regulates interdigital cell death by a ROS-mediated mechanism

Vascular patterning regulates interdigital cell death by a ROS-mediated mechanism

The Alpha Thalassaemias

Alpha-thalassémie majeure : à propos d’un cas de dépistage anténatal et revue de la littérature

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