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Case Reports
. 2021 May;185(5):1509-1514.
doi: 10.1002/ajmg.a.62111. Epub 2021 Feb 5.

Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2-opathy

Enrica Marchionni  1 , Emanuele Agolini  2 , Gioia Mastromoro  1 , Daniele Guadagnolo  1 , Giulia Coppola  3 , Mario Roggini  4 , Mara Riminucci  3 , Antonio Novelli  2 , Antonella Giancotti  5 , Alessandro Corsi  3 , Antonio Pizzuti  1   6
Affiliations
Case Reports

Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2-opathy

Enrica Marchionni et al. Am J Med Genet A. 2021 May.

Abstract

BICD2 (BICD Cargo Adaptor 2, MIM*609797) mutations are associated with severe prenatal-onset forms of spinal muscular atrophy, lower extremity-predominant 2B (SMALED2B MIM 618291) or milder forms with childhood-onset (SMALED2A MIM 615290). Etiopathogenesis is not fully clarified and a wide spectrum of phenotypic presentations is reported, ranging from extreme prenatal forms with adverse outcome, to slow progressive late-onset forms. We report a fetus at 22 gestational weeks with evidence of Arthrogryposis Multiplex Congenita on ultrasound, presenting with fixed extended lower limbs and flexed upper limbs, bilateral clubfoot and absent fetal movements. A trio-based prenatal Exome Sequencing was performed, disclosing a de novo heterozygous pathogenic in frame deletion (NM_015250.3: c.1636_1638delAAT; p.Asn546del) in BICD2. After pregnancy termination, quantitative analysis on NeuN immunostained spinal cord sections of the ventral horns, revealed that neuronal density was markedly reduced compared to the one of an age-matched normal fetus and an age-matched type-I Spinal Muscular Atrophy sample, used as a comparative model. The present case, the first prenatally diagnosed and neuropathologically characterized, showed an early motor neuron loss in SMALED2B, providing further insight into the pathological basis of BICD2-opathies.

Keywords: BICD2; SMALED2B; exome sequencing; motor neurons; prenatal diagnosis.

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