Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms

Abstract

Background: Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation: A Chinese family with two offspring-patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions: This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.

A Novel Homozygous VPS13B Splice-Site Mutation Causing the Skipping of Exon 38 in a Chinese Family With Cohen Syndrome

“…CS is less frequent among Chinese population with only several cases reported to date. In 2019, two CS siblings from Chinese healthy, non-consanguineous parents exhibited mental retardation, speech delay, microcephaly, generalized joint hyper extensibility, hypotonia, thick hair, thick eyebrows, prominent upper central incisors, and hyperlinear palms (14). Hyperlinear palms is an additional phenotypic characteristic of CS only described in Chinese population and the clinical features of our patient have confirmed this.…”

“…CS is relatively common among Finnish population in spite of the low prevalence worldwide (5). Apart from this, CS has also been reported in Indian, Jordanian, Chinese, Saudi, Tunisian, Iranian, German, Syrian, Lebanese, and Pakistani (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

“…In addition, VPS13B is also responsible for autism spectrum disorders (ASDs) (18). VPS13B is localized on chromosome 8 (8q22.2) with 62 exons and encodes a 4022-amino acid transmembrane protein (14). The encoded protein is a Golgi-associated peripheral membrane protein that plays an important role in Golgi integrity and homeostasis, and membrane transport (17,19), and it belongs to the VPS13 protein family, which are highly conserved in eukaryotic cells (20,21).…”

A VPS13B mutation in Cohen syndrome presented with petechiae: An unusual presentation

“…They are wave‐shaped and downward slanting with thick eyebrows and eyelashes 7 . In few cases such as a Chinese patient with CS, hyperlinear palms or palms with extra skin creases displayed a hand phenomenon with atopic dermatitis or ichthyosis Vulgaris 8 . But in our case, skin manifestations have been demonstrated in a different shape in a way that we discovered some tiny petechial spots on her lower limbs without any itching and irritation.…”

Co-existence of Cohen Syndrome and Pendred Syndrome? Diagnostic Challenges Associated With Presence of Multiple Genomic Variants in the Newborn: A Case Report

“…The weight of patient won't increase because of the poor feeding caused by muscular hypotonia, so infant patients often show poor weight gain rather than typical facial features [17]. Just one case of bilateral strabismus in CS was reported in China [18], However, due to the absence of fundus examination and obvious clinical heterogeneity among patients with CS, it is impossible to determine whether there is damage to photoreceptor cilia and integrity of retinal structure [19]. So we can't judge whether strabismus is one of the manifestation of CS.…”