An infant with congenital respiratory insufficiency and diaphragmatic paralysis: A novel BICD2 phenotype?

Autor: Chin HL; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore, Singapore., Huynh S; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada., Ashkani J; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Castaldo M; Division of Neonatology, Department of Pediatrics, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada., Dixon K; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Selby K; Division of Neurology, Department of Pediatrics, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada., Shen Y; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada., Wright M; Division of Respirology, Department of Pediatrics, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada., Boerkoel CF; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada., Hendson G; Department of Pathology, BC Children's Hospital, BC Women's Hospital and Health Centre, Vancouver, British Columbia, Canada., Jones SJM; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.; Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2022 Mar; Vol. 188 (3), pp. 926-930. Date of Electronic Publication: 2021 Nov 26.
DOI: 10.1002/ajmg.a.62578
Abstrakt: Monoallelic pathogenic variants in BICD2 are associated with autosomal dominant Spinal Muscular Atrophy Lower Extremity Predominant 2A and 2B (SMALED2A, SMALED2B). As part of the cellular vesicular transport, complex BICD2 facilitates the flow of constitutive secretory cargoes from the trans-Golgi network, and its dysfunction results in motor neuron loss. The reported phenotypes among patients with SMALED2A and SMALED2B range from a congenital onset disorder of respiratory insufficiency, arthrogryposis, and proximal or distal limb weakness to an adult-onset disorder of limb weakness and contractures. We report an infant with congenital respiratory insufficiency requiring mechanical ventilation, congenital diaphragmatic paralysis, decreased lung volume, and single finger camptodactyly. The infant displayed appropriate antigravity limb movements but had radiological, electrophysiological, and histopathological evidence of myopathy. Exome sequencing and long-read whole-genome sequencing detected a novel de novo BICD2 variant (NM_001003800.1:c.[1543G>A];[=]). This is predicted to encode p.(Glu515Lys); p.Glu515 is located in the coiled-coil 2 mutation hotspot. We hypothesize that this novel phenotype of diaphragmatic paralysis without clear appendicular muscle weakness and contractures of large joints is a presentation of BICD2-related disease.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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