Severe SOPH syndrome due to a novel NBAS mutation in a 27‐year‐old woman—Review of this pleiotropic, autosomal recessive disorder: Mystery solved after two decades

Abstract

Autosomal recessive SOPH syndrome was first described in the Yakuts population of Asia by Maksimova et al. in 2010. It arises from biallelic pathogenic variants in the NBAS gene and is characterized by severe postnatal growth retardation, senile facial appearance, small hands and feet, optic atrophy with loss of visual acuity and color vision, and normal intelligence (OMIM #614800). The presence of Pelger-Hüet anomaly in this disorder led to its name as an acronym for Short stature, Optic nerve atrophy, and Pelger-Hüet anomaly. Recent publications have further contributed to the characterization of this syndrome through additional phenotype-genotype correlations. We review the clinical features described in these publications and report on a 27-year-old woman with dwarfism with osteolysis and multiple skeletal problems, minor anomalies, immunodeficiency, diabetes mellitus, and multiple secondary medical problems. Her condition was considered an unknown autosomal recessive disorder for many years until exome sequencing provided the diagnosis by revealing a founder disease-causing variant that was compound heterozygous with a novel pathogenic variant in NBAS. Based on the major clinical features of this individual and others reported earlier, a revision of the acronym is warranted to facilitate clinical recognition.

Origins of SOPH syndrome: A study of 93 Yakut patients with review of C‐terminal phenotype

“…We strived to perform a comparative analysis between the phenotypes of SOPH patients and carriers of the p. Arg1914His variant in the compound heterozygous state. In total, we have found the descriptions of 17 cases with compound heterozygosity in the available literature 6,10‐16 . Genetic variants other than p. Arg1914His in the NBAS gene included 1 missense, 7 nonsense, 4 frameshift, 3 splice‐site variants, and 2 long in‐frame deletions.…”

“…We strived to perform a comparative analysis between the phenotypes of SOPH patients and carriers of the p. Arg1914His variant in the compound heterozygous state. In total, we have found the descriptions of 17 cases with compound heterozygosity in the available literature 6,[10][11][12][13][14][15][16] . We did not find any specific traits regarding the cardiovascular, endocrinological, and the hematopoietic systems.…”