Prenatal ultrasound diagnosis of amelia

Rijhsinghani, Asha; Yankowitz, Jerome; Mazursky, Jon E.; Williamson, Roger A.

doi:10.1002/pd.1970150711

Cited by 8 publications

(2 citation statements)

References 8 publications

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“…Interestingly, tetra-amelia seems to be compatible with life [51], whereas the tetradysmelic animals were stillborn. One reason for this difference might be that dystocia as a result of missing limbs, which are important for successful initiation of birth in cattle [52], occurs only in cattle and not in humans.…”

Section: Discussionmentioning

confidence: 99%

A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle

et al. 2020

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Background Tetradysmelia is a rare genetic disorder that is characterized by an extremely severe reduction of all limb parts distal of the scapula and pelvic girdle. We studied a Holstein Friesian backcross family with 24 offspring, among which six calves displayed autosomal recessive tetradysmelia. In order to identify the genetic basis of the disorder, we genotyped three affected calves, five dams and nine unaffected siblings using a Bovine Illumina 50 k BeadChip and sequenced the whole genome of the sire. Results Pathological examination of four tetradysmelia cases revealed a uniform and severe dysmelia of all limbs. Applying a homozygosity mapping approach, we identified a homozygous region of 10.54 Mb on chromosome 14 (Bos taurus BTA14). Only calves that were diagnosed with tetradysmelia shared a distinct homozygous haplotype for this region. We sequenced the whole genome of the cases’ sire and searched for heterozygous single nucleotide polymorphisms (SNPs) and small variants on BTA14 that were uniquely present in the sire and absent from 3102 control whole-genome sequences of the 1000 Bull Genomes Project, but none were identified in the 10.54-Mb candidate region on BTA14. Therefore, we subsequently performed a more comprehensive analysis by also considering structural variants and detected a 50-kb deletion in the targeted chromosomal region that was in the heterozygous state in the cases’ sire. Using PCR, we confirmed that this detected deletion segregated perfectly within the family with tetradysmelia. The deletion spanned three exons of the bovine R-spondin 2 (RSPO2) gene, which encode three domains of the respective protein. R-spondin 2 is a secreted ligand of leucine-rich repeats containing G protein-coupled receptors that enhance Wnt signalling and is involved in a broad range of developmental processes during embryogenesis. Conclusions We identified a 50-kb deletion on BTA14 that disrupts the coding sequence of the RSPO2 gene and is associated with bovine tetradysmelia. To our knowledge, this is the first reported candidate causal mutation for tetradysmelia in a large animal model. Since signalling pathways involved in limb development are conserved across species, the observed inherited defect may serve as a model to further elucidate fundamental pathways of limb development.

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Section: Discussionmentioning

confidence: 99%

A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle

et al. 2020

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“…The prevalence of bilateral lower limb aplasia is 0.4/100 000 (4). Cases with limb/pelvis hypoplasia/aplasia were first reported by Al-Awadi et al (1).…”

Section: Discussionmentioning

confidence: 99%

Al-Awadi/Raas-Rothschild Syndrome in a Newborn with Additional Anomalies

Alp

Alp²,

Atabek³

et al. 2010

JCRPE

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Al-Awadi/Raas-Rothschild (AARR) syndrome is a rare phocomelia syndrome characterized by limb/pelvic hypoplasia/aplasia, renal anomalies such as horseshoe and polycystic kidney, and abnormal facial features including cleft palate, hypertelorism and micro-retrognatia. Autosomal recessive inheritance has been proposed for AARR syndrome. In this report a boy affected with AARR syndrome is presented. The previous pregnancy of the mother was terminated because of lower limb agenesis detected at 14th week of gestation. This report emphasizes the importance of recognizing severe pelvic and limb deficiencies in newborns with AARR syndrome and differentiating the syndrome from other multiple malformation syndromes. Fetal ultrasonography at 15th week of gestation is helpful in diagnosing the major extremity anomalies in the fetus.Conflict of interest:None declared.

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Pre‐ and postnatal diagnosis of limb anomalies: A series of 107 cases

Holder‐Espinasse

Devisme

Thomas

et al. 2003

American J of Med Genetics Pt A

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This is a 3-year retrospective study of 107 cases presenting with limb anomalies detected either on prenatal ultrasound scan, or after birth. These limb malformations are developmental anomalies, and can be isolated, syndromic, or associated with multiple malformations. Cases were ascertained through the prenatal diagnosis center, the pediatrics department, and the feto-pathology department. Several criteria were analyzed including sex ratio, prenatal diagnosis, karyotype, termination of pregnancies, clinical or pathological examination, pediatric or surgical and/or genetic assessment, and whether or not a diagnosis was made. Positional deformities and syndactyly were excluded. Limb anomalies were detected prenatally in 45% of the cases, and a diagnosis was made in 78%, including isolated, syndromic, or chromosomal anomalies. Sixty-one per cent of the infants had follow-up, either pediatric, surgical, or genetic. Prenatal multidisciplinary assessment is fundamental to assist with counseling, as is the post-natal follow-up of the infant. The diagnosis, if made, will obviously influence the information that will be given to the parents and the management of the malformation. If the pregnancy is terminated, feto-pathological examination is essential to help make a diagnosis, and guide recurrence risks. We are currently undertaking a prospective study, and we will develop a protocol of investigations in the future, depending on the type of the malformation identified.

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Prenatal ultrasound diagnosis of amelia

Abstract: Amelia is a very rare form of limb reduction defect. The incidence of isolated amelia with or without other limb reductions is 0.4 per 100,000 births. We report a cluster of three cases diagnosed prenatally. One was isolated tri-amelia and two were isolated tetra-amelia.

Cited by 8 publications

References 8 publications

A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle

A 50-kb deletion disrupting the RSPO2 gene is associated with tetradysmelia in Holstein Friesian cattle

Al-Awadi/Raas-Rothschild Syndrome in a Newborn with Additional Anomalies

Pre‐ and postnatal diagnosis of limb anomalies: A series of 107 cases

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