Genetic analysis of the ALMS1 gene in two families affected with Alstr?m syndrome / 中华眼底病杂志

Objective:To identify two pathogenic gene mutations in two families with Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. Two patients and five family members from two Han families of ALMS diagnosed at Henan Eye Hospital from August 2020 to December 2021 were enrolled in this study. All participants underwent comprehensive ophthalmic examinations including best corrected visual acuity (BCVA), color test, slit-lamp, fundus biomicroscopy with slit lamp, fundus color photography, optical coherence tomography (OCT) and full-field electroretinography (ff-ERG) after the detailed history of the patient was taken. Five millilitres peripheral venous blood of each subject was collected, and the whole genome DNA was extracted. The pathogenic genes and mutation sites were identified using whole exome sequencing and the identified mutations were verified by Sanger sequencing. Mutation sites were analyzed via bioinformatics softwares.Results:Family one included one victim and two members and family two included one victim and three members. Proband in the first family was a four-year old boy whose chief complaint was poor vision along with photophobia since born, while proband in the second family was a 12-year old girl whose chief complaint was the same. The boy proband could not distinguish color, and both the anterior segment and fundus were normal. Ellipsoid zone of the boy was unclear in both eyes in OCT, and though rod system function decreased mildly-moderately in both eyes, the cone system function decreased severely in ff-ERG. The girl could not distinguish color as well, and the anterior segment was normal, though obvious pigmentary change could be seen in both retinas. The integrity of outer retinal bands was unclear in both eyes in OCT, and both cone and rod systems function decreased severely in both eyes in ff-ERG. Gene tests and bioinformatics analyze showed c.468dupT and c.10819C>T of ALMS1 gene in family one were novel mutations and c.10819C>T in family one and c.10831_10832del in family two were pathogenic mutations. Conclusions:M1, M2 and M3, M4 may be pathogenic gene variants in family 1 and family 2, respectively. The compound heterozygous mutation, c.468dupT and c.10819C>T of ALMS1 gene was a novel mutation.

Introduction and interpretation of European clinical management guidelines for Alstr?m syndrome in 2020 / 中华实用儿科临床杂志

Alstr?m syndrome is a rare multisystem genetic disease caused by mutations in the ALMS1 gene.Both of its clinical diagnosis and treatment are very difficult.In 2020, the Consensus Clinical Management Guidelines for Alstr?m Syndrome, developed with the participation of many countries, was published in the Orphanet Journal of Rare Diseases.A systematic literature review on Alstr?m syndrome of the last 45 years until October 2019 was carried out and then the clinical management guideline for Alstr?m syndrome was proposed.In this report, the contents of the 2020 European guideline for Alstr?m syndrome would be introduced briefly with appropriate interpretation in order to provide reference.

Progress in pathogenesis, diagnosis, and treatment of Alstrom syndrome / 国际儿科学杂志

Alstrom syndrome (ALMS) is a rare autosomal recessive disorder involving multiple systems.The main clinical manifestations include nystagmus,hearing loss,obesity,insulin resistance,type 2 diabetes,dilated cardiomyopathy,etc.Primary cilia are key organelles.ALMS is classified as a ciliopathy,mainly related to the mutation of ALMS1 gene which affects cilia function,but the specific mechanism remains unclear.At present,the diagnosis of ALMS mainly relies on clinical manifestations and gene sequencing.There are no specific and effective treatment methods except for symptomatic treatment,but early diagnosis and intervention can delay disease progression and improve patients' quality of life.This article reviews recent advances in the pathogenesis,diagnosis,and treatment of ALMS.

Progress in pathogenesis, diagnosis, and treatment of Alstrom syndrome / 国际儿科学杂志

Alstrom syndrome(ALMS)is a rare autosomal recessive disorder involving multiple systems.The main clinical manifestations include nystagmus, hearing loss, obesity, insulin resistance, type 2 diabetes, dilated cardiomyopathy, etc.Primary cilia are key organelles.ALMS is classified as a ciliopathy, mainly related to the mutation of ALMS1 gene which affects cilia function, but the specific mechanism remains unclear.At present, the diagnosis of ALMS mainly relies on clinical manifestations and gene sequencing.There are no specific and effective treatment methods except for symptomatic treatment, but early diagnosis and intervention can delay disease progression and improve patients′ quality of life.This article reviews recent advances in the pathogenesis, diagnosis, and treatment of ALMS.

Alstrom syndrome in children:a case report and literature review / 临床儿科杂志

Objective To analyze the clinical feature, diagnosis and treatment of Alstrom syndrome. Method The clinical data of a case of Alstrom syndrome and the result of her ALMS1 sequencing by the two generation sequencing were retrospectively reviewed. Results The 12 year and 10 month old female suffered from dilated cardiomyopathy, obesity, optic nerve diseases, sensorineural hearing loss, high blood glucose and irregular menstruation since one month of birth. Laboratory examination showed she had high testosterone level, hyperglycemia, hyperlipidemia and fatty liver. High-throughput sequencing confirmed there was ALMS1 gene mutation which includes hybrid frameshift mutations of c.5418delC and p.Y1807Tfs*23, and heterozygous nonsense mutation of c.10549C>T and p.Q3517*, and c.5418delC was a new variation reported for the first time. Conclusion Alstrom syndrome is an autosomal recessive genetic disease, which is characterized by multiple organ dysfunction and metabolic syndrome, and can be diagnosed by gene detection.