Concurrent OPA1 mutation and chromosome 3q deletion leading to Behr syndrome: a case report
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CASE REPORT
Open Access
Concurrent OPA1 mutation and chromosome 3q deletion leading to Behr syndrome: a case report Ting Zeng1,2, Linyan Liao1, Yi Guo1, Xuxu Liu1, Xiaobo Xiong1, Yu Zhang1,2, Shi Cen1,2, Honghui Li1,2 and Shuzhang Wei1,2*
Abstract Background: Optic atrophy 1 (OPA1) gene mutations are associated with dominantly inherited optic neuropathy resulting in a progressive loss of visual acuity. Compound heterozygous or homozygous variants that lead to severe phenotypes, including Behr syndrome, have been reported rarely. Case presentation: Here, we present a 14-month-old boy with early onset optic atrophy, congenital cataracts, neuromuscular disorders, mental retardation, and developmental delay. Combined genetic testing, including whole exome sequencing (WES) and chromosomal microarray analysis, revealed a concurrent OPA1 variant (c.2189 T > C p.Leu730Ser) and de novo chromosome 3q deletion as pathogenic variants leading to the severe phenotype. Conclusions: Our case is the first reporting a novel missense OPA1 variant co-occurring with a chromosomal microdeletion leading to a severe phenotype reminiscent of Behr syndrome. This expands the mutation spectrum of OPA1 and inheritance patterns of this disease. Keywords: OPA1, Optic atrophy, Behr syndrome, Microdeletion, Case report
Background The optic atrophy 1 (OPA1) gene encodes a dynaminrelated protein located within the mitochondrial inner membrane, and is involved in multiple critical cellular and mitochondrial functions [1]. Variants in the OPA1 gene are mostly related with autosomal dominant optic atrophy (DOA) (OMIM#165500) [2–5]. This disorder is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecalscotoma of variable density. Dominant optic atrophy plus (DOA+) syndrome is observed in 20% of patients with pathogenic OPA1 variants [4–6], * Correspondence: [email protected] 1 Department of Child Healthcare, Liuzhou Maternity and Child Healthcare Hospital, 50 Boyuan Avenue, Liuzhou 545616, China 2 Key Laboratory of Developmental Disorders in Children, Liuzhou Maternity and Child Healthcare Hospital, 50 Boyuan Avenue, Liuzhou 545616, China
manifesting extra-neuromuscular features like ataxia, myopathy, peripheral neuropathy, sensorineural deafness, and chronic progressive external ophthalmoplegia. To date, over 500 pathogenic variants have been documented in OPA1 genes that are inherited in a dominant manner, with an estimated prevalence at 1/50,000 [7]. OPA1 variants with a recessive inheritance mode that cause the Behr syndrome have been recently revealed in a few cases with early-onset optic atrophy [8, 9], spinocerebellar degeneration, mental retardation, and developmental delay [10]. Clinical heterogeneity has been observed in patients with compound heterozygous or homozygous variants of the OPA1 gene [11]. Here, we report a boy with a hemizygous OPA1 variant unmasked by concurrent chromosome 3q deletion. Th
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