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Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2 ‐opathy
Author(s) -
Marchionni Enrica,
Agolini Emanuele,
Mastromoro Gioia,
Guadagnolo Daniele,
Coppola Giulia,
Roggini Mario,
Riminucci Mara,
Novelli Antonio,
Giancotti Antonella,
Corsi Alessandro,
Pizzuti Antonio
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62111
Subject(s) - spinal muscular atrophy , fetus , exome sequencing , arthrogryposis , lower motor neuron , medicine , progressive muscular atrophy , atrophy , motor neuron , spinal cord , upper motor neuron , pathology , anatomy , pregnancy , biology , phenotype , neuroscience , amyotrophic lateral sclerosis , genetics , disease , gene
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.