Whole genome sequencing identifies a novel ALMS1 gene mutation in two Chinese siblings with Alström syndrome

Yang, Lin; Li, Zixiu; Mei, Mei; Fan, Xiaomei; Zhan, Guodong; Wang, Huijun; Huang, Guoying; Wang, Mingbang; Tian, Weidong; Zhou, Wenhao

doi:10.1186/s12881-017-0418-3

Cited by 10 publications

(4 citation statements)

References 16 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As of now, there are more than 250 different types AS causative ALMS1 mutations identified, of which 96% belongs to frameshift or nonsense category. Most of the ALMS1 mutation data has come from Alstrom syndrome patients belonging to non-Arab ethnic backgrounds (Castro et al, 2018, Tsai et al, 2018, Kilinc et al, 2018, Casey et al, 2014, Kim et al, 2015, Yang et al, 2017, Brofferio et al, 2017, Das Bhowmik et al, 2017). The high rate of consanguinity enriches the occurrence of defective alleles in inbred populations like Arabs and might sometime present novel disease causative alleles.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

Kamal

Sahly

Banaganapalli

et al. 2020

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Alström syndrome (AS, OMIM ID 203800) is a rare childhood multiorgan disorder, which is widely studied in non-Arab ethnic patients. The clinical and molecular basis of AS and the mode of disease inheritance in consanguineous Arab populations is not well investigated. Therefore, to identify the molecular basis of AS in familial forms, the present study performed whole exome sequencing of 5 AS patients belonging to 2 different Bedouin families from Saudi Arabia. The present study identified the AS causative rare biallelic mutations in ALMS gene:T376S in exon 5 and S909* in exon 8 for family A and an R2721* in exon 10 (R2721*) for family B. ALMS1 targeted genetic sequencing of healthy population controls and family members has confirmed its extremely rare frequency and autosomal recessive mode of inheritance. The truncating mutations S909* and R2721* could cause the loss of CC domains and ALMS motif on C-terminal end of the protein and creates unstable protein, which eventually undergoes intracellular degradation. The premature protein truncating mutations described in our study may eventually provide further insight into the functional domains of the ALMS1 protein and contribute to the understanding of the phenotypic spectrum of AS. Whole exome sequencing based molecular diagnosis is expected to rule out ambiguity surrounding clinical diagnosis of suspected AS cases.

show abstract

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

Kamal

Sahly

Banaganapalli

et al. 2020

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

show abstract

“…About one-third of patients with AS are completely blind by 9 years of age, 50% by 12 years of age, and 90% by 16 years of age[ 8 ]. In a study of 21 Chinese patients with AS, 100% of them had poor vision, 19% had nervous system impairment, and 14% had liver and kidney dysfunction by the age of 36 mo, similar to populations in Europe and the United States[ 35 , 36 ]. About two-thirds of patients with AS will develop DCM, and their cardiac function will improve at 3 years of age and remain stable under the “low normal” condition[ 8 ].…”

Section: Discussionmentioning

confidence: 91%

Alström syndrome with a novel mutation of ALMS1 and Graves’ hyperthyroidism: A case report and review of the literature

Zhang¹,

Wang²,

Sun³

et al. 2021

WJCC

View full text Add to dashboard Cite

BACKGROUND Alström syndrome (AS, OMIM ID 203800) is a rare disease involving multiple organs in children and is mostly reported in non-Chinese patients. In the Chinese population, there are few reports on the clinical manifestations and pathogenesis of AS. This is the first report on the association between AS and Graves’ hyperthyroidism. CASE SUMMARY An 8-year-old Chinese girl was diagnosed with AS. Two years later, Graves’ hyperthyroidism developed with progressive liver dysfunction. The patient’s clinical data were collected; DNA from peripheral blood of the proband, parents and sibling was collected for gene mutation detection using the second-generation sequencing method and gene panel for diabetes. The association between the patient’s genotype and clinical phenotype was analyzed. She carried the pathogenic compound heterozygous mutation of ALMS1 (c.2296_2299del4 and c.11460C>A). These stop-gain mutations likely caused truncation of the ALMS1 protein. CONCLUSION The manifestation of hyperthyroidism may suggest rapid progression of AS.

show abstract

“…To better understand the commonality of those 37 variants, we summarized the variants reported by other Chinese cohorts and cohorts from other countries. We retrieved 24 Chinese ALMS patients from 22 families from the literature ( Liu et al, 2009 ; Liang et al, 2013 ; Wang et al, 2015 ; Xu et al, 2016 ; Yang et al, 2017 ; Rethanavelu et al, 2020 ; Zhou et al, 2020 ). All variants of the ALMS1 gene from 69 Chinese families are summarized in Table 3 and the distribution of these variants in Chinese and other countries’ cohorts are shown in Figure 2B .…”

Section: Resultsmentioning

confidence: 99%

Molecular and Phenotypic Expansion of Alström Syndrome in Chinese Patients

et al. 2022

View full text Add to dashboard Cite

Alström syndrome (ALMS) is a rare inherited metabolic disease and ciliopathy. Large cohorts of ALMS are lacking around the world. Detailed genetic and phenotypic data were obtained from all affected individuals. Olfactory function was evaluated by the Chinese Smell Identification Test and facial pattern was analyzed with Face2gene. Fifty ALMS patients were included in this study, aged from 0.3 to 21.7 years old. Sixty-one ALMS1 variants in 50 patients from 47 different families were confirmed, including 59 truncating and two exon deletions. Twenty-four of those variants were novel. We also summarized all previously reported cases of Chinese ALMS patients (69 patients) and identified specific and common variants within the Chinese population. Besides, the Chinese Smell Identification Test scores in patients was lower than that in controls (11.97 Vs. 10.44, p < .05), indicating olfactory identification impairments in ALMS patients. The facial pattern in ALMS patients was also distinctive from that of the controls (p < .05). In conclusion, this is the largest cohort of Chinese ALMS patients. We have successfully identified both specific and common variants in our cohort. We found a new phenotype of olfactory impairments in ALMS patients through a case-control study.

show abstract

Whole genome sequencing identifies a novel ALMS1 gene mutation in two Chinese siblings with Alström syndrome

Cited by 10 publications

References 16 publications

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

Alström syndrome with a novel mutation of ALMS1 and Graves’ hyperthyroidism: A case report and review of the literature

Molecular and Phenotypic Expansion of Alström Syndrome in Chinese Patients

Contact Info

Product

Resources

About