Novel mutation in Hermansky–Pudlak syndrome type 2 with mild immunological phenotype

Abstract Background To identify the gene mutation in a Chinese family with Usher syndrome type 2 and describe the clinical features. Methods A 23-year-old man complain of 10-year nyctalopia and a 3-year decline in visual acuity in both eyes accompanied by congenital dysaudia. To clarify the diagnosis, the clinical symptoms of the patient were observed and analysed in combination with comprehensive ophthalmologic examinations as well as genetic analysis(Targeted exome sequencing, TES). Results Typical clinical presentation of Usher syndrome on fundus features was found, which included a wax yellow-like disc, bone-spicule formations, and retinal vessel stenosis. Optical coherence tomography(OCT) and optical coherence tomography angiography (OCTA) showed loss of the ellipsoid zone and a reduction in paracaval vessel density in both eyes. Genetic analysis identified the presence of novel homozygote of c.8483_8486del (p.S2828fs) in USH2A, a gene responsible for Usher syndrome type 2 (OMIM:276901). This novel mutation in USH2A led to premature translation termination, resulting in the deletion of 19 fibronectin type 3 domains(FN3), which plays an important role in protein binding. Based on the clinical manifestations and genetic result, the patient was diagnosed with Usher syndrome type 2. Conclusions We found a novel mutation of c.8483_8486del in USH2A gene through TES techniques for 381 inherited retinal disease (IRD) related genes. The results of this study broaden the spectrum of mutations in Usher syndrome type 2 and suggest that the combination of TES molecular diagnosis and clinical information can help USH patients obtain a better diagnoses.

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Primary immunodeficiency associated with hypopigmentation: A differential diagnosis approach

Allergologia et Immunopathologia ◽

10.15586/aei.v49i2.61 ◽

2021 ◽

Vol 49 (2) ◽

pp. 178-190

Author(s):

Raha Zamani ◽

Sepideh Shahkarami ◽

Nima Rezaei

Keyword(s):

Primary Immunodeficiency ◽

Treatment Options ◽

Genetic Diseases ◽

Endosomal Trafficking ◽

Syndrome Type ◽

Griscelli Syndrome ◽

Hermansky Pudlak Syndrome ◽

Chediak Higashi Syndrome ◽

Prompt Diagnosis

Primary immunodeficiency diseases (PIDs) are a group of more than 400 disorders representing aberrant functioning or development of immune system. Hypopigmentation syndromes also characterize a distinguished cluster of diseases. However, hypopigmentation may also signify a feature of genetic diseases associated with immunodeficiency, such as Chediak–Higashi syndrome, Griscelli syndrome type 2, Hermansky–Pudlak syndrome type 2 and type 10, Vici syndrome, and P14/LAMTOR2 deficiency, all of which are linked with dysfunction in vesicular/endosomal trafficking. Regarding the highly overlapping features, these disorders need a comprehensive examination for prompt diagnosis and effective management. As an aid to clinician, distinguishing the pathophysiology, clinical phenotype, and diagnosis as well as treatment options of the six mentioned PID disorders associated with hypopigmentation are described and discussed in this review.

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A novel mutation in FAM111A gene in child with Kenny-Caffey syndrome type 2 presenting with short statue, medullary stenosis and hypoparathyroidism

Bone Abstracts ◽

10.1530/boneabs.7.p119 ◽

2019 ◽

Author(s):

Khomsak Srilanchakon ◽

Vichit Supornsilchai ◽

Kanya Suphapeetiporn

Keyword(s):

Novel Mutation ◽

Syndrome Type

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