Analysis of the ocular clinical features and pathogenic genes in patients with Alstr?m syndrome
10.3760/cma.j.cn511434-20221018-00552
- VernacularTitle:Alstr?m综合征患者眼部临床特征和致病基因分析
- Author:
Weiwei LIU
1
;
Yingying CHU
;
Hui WANG
;
Fei WANG
;
Ruixue CHU
;
Xiantao SUN
;
Yuebing LU
;
Jifeng YU
Author Information
1. 郑州大学附属儿童医院 河南省儿童医院 郑州儿童医院眼科, 郑州 450000
- Keywords:
Alstr?m syndrome;
Cone-rod dystrophy;
ALMS1 mutations
- From:
Chinese Journal of Ocular Fundus Diseases
2023;39(7):530-537
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.
