Expanding the genetic spectrum of ALKU syndrome: Compound heterozygosity for two deleterious variants in SMG8 gene

• Tipo: Outra Publicação em Revista Científica Internacional
• Data: 2023

Autores

Fernandes, AA (Autor) Outra; Grangeia, A (Autor) FMUP; Dias, L (Autor) Outra; Guimaraes, J (Autor) Outra

Revista

Título: American Journal of Medical Genetics, Part A

ISSN: 1552-4825

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 0 Citações

Scopus

Outras Informações

ID Authenticus: P-00Y-ENF

DOI: 10.1002/ajmg.a.63242

Abstract (EN): Alzahrani-Kuwahara syndrome (ALKUS) is a neurodevelopmental disorder that includes microcephaly, facial dysmorphism, and variable congenital and eye malformations. We present the first case of ALKUS described in the European population caused by two variants in compound heterozygosity of the gene SMG8. We present a patient with two variants in compound heterozygosity in the SMG8 gene identified by in trio whole exome sequencing based in next generation sequencing (xGEN (R) Exome Research Panel, Nextseq550 platform). International case reporting (CARE) criteria were followed. Patient written consent was obtained through legal responsible persons. We describe a 27-year-old male, the second child of a healthy and non-consanguineous couple, whose genetic analysis showed two variants in compound heterozygosity, c.1159C > T (p.Arg387*) and c.2407del (p.Arg803Glyfs*10), in the SMG8 gene, both classified as likely pathogenic. As described by Fatema Alzahrani et al. in a series of eight patients, our patient had global developmental delay with impaired intellectual development, facial dysmorphism, and limb disproportion. Additionally, our patient had lower limb spastic paraparesis, marked osteotendinous hyperreflexia with extensor plantar response bilaterally and paretic gait. Our patient resembles the phenotype described by Fatema Alzahrani et al., however, he is the first patient with two SMG8 deleterious variants in compound heterozygosity, and the first to exhibit pyramidal signs and gait disorder as part of the phenotype.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5