Novel homozygous LAMB1 in-frame deletion in a pediatric patient with brain anomalies and cerebrovascular event

• Published in: American journal of medical genetics. Part A Vol. 191; no. 10; pp. 2656 - 2663
• Main Authors: Toutouna, Louiza, Beck-Woedl, Stefanie, Feige, Ursula, Glaeser, Birgitta, Komlosi, Katalin, Eckenweiler, Matthias, Luetzen, Niklas, Haack, Tobias B, Fischer, Judith, Bader, Ingrid, Tzschach, Andreas
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2023
• Subjects: Cerebellum; Corpus callosum; Epidermal growth factor; Epilepsy; Exons; Gene deletion; Hydrocephalus; Lissencephaly; Magnetic resonance imaging; Neuroimaging; Patients; Pediatrics; microcephaly; developmental delay; structural brain anomalies; lissencephaly; LAMB1; autosomal recessive
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.63349

Biallelic pathogenic variants in LAMB1 have been associated with autosomal recessive lissencephaly 5 (OMIM 615191), which is characterized by brain malformations (cobblestone lissencephaly, hydrocephalus), developmental delay, and epilepsy. Pathogenic variants in LAMB1 are rare, with only 11 pathogenic variants and 11 patients reported to date. Here, we report on a 6-year-old patient from a consanguineous family with profound developmental delay, microcephaly, and a history of a perinatal cerebrovascular event. Brain magnetic resonance imaging (MRI) showed cerebellar cystic defects, signal intensity abnormalities, and a hypoplastic corpus callosum. Trio-exome analysis revealed a homozygous in-frame deletion of Exons 23 and 24 of LAMB1 affecting 104 amino acids including the epidermal growth factor (EGF)-like units 11 and 12 in Domain III. To our knowledge, this is the first reported in-frame deletion in LAMB1. Our findings broaden the clinical and molecular spectrum of LAMB1-associated syndromes.