Dataset Information

A novel variant in ALMS1 in a patient with Alstrom syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review.

ABSTRACT: Alström syndrome (AS) is a type of monogenic syndromic ciliopathy disease. The main clinical features of AS include cone?rod malnutrition, sensorineural hearing loss, metabolic dysfunctions and multiple organ failure, which are caused by mutations of Alström syndrome protein 1 (ALMS1) gene. The current study aimed to identify pathogenic variants in a Chinese patient with AS and to review the relevant literature. Genomic DNA extracted from a 10?year?old male with AS was evaluated using a disease?targeted gene panel. According to the bioinformatics analysis, the current study identified a novel frameshift mutation in exon 8 (c.2988_2989del, p.T996fs) and a rare nonsense mutation in exon 10 (c.9535C>T, p.R3179*) of the ALMS1 gene. Both parents were heterozygous carriers of this gene. To the best of our knowledge, these mutations have not been reported in normal population databases. According to the criteria of the American College of Medical Genetics and Genomics, the mutations were pathogenic. Based on these findings, amniotic fluid sample was used for prenatal diagnosis of the couple's fetus, and it was observed that the fetus carried c.9535C>T, and not c.2988del. During the follow?up duration of >2 years of the fetus, it was confirmed that he was a healthy male. The results of the present study identified two compound heterozygous ALMS1 mutations in a patient with the symptoms of Alström syndrome and reported a novel ALMS1 variant which expands the spectrum of ALMS1 variants in AS.

SUBMITTER: Zhou C

PROVIDER: S-EPMC7453607 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel variant in ALMS1 in a patient with Alström syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review.

Zhou Cong C Xiao Yuanyuan Y Xie Hanbing H Liu Shanling S Wang Jing J

Molecular medicine reports 20200731 4

Alström syndrome (AS) is a type of monogenic syndromic ciliopathy disease. The main clinical features of AS include cone‑rod malnutrition, sensorineural hearing loss, metabolic dysfunctions and multiple organ failure, which are caused by mutations of Alström syndrome protein 1 (ALMS1) gene. The current study aimed to identify pathogenic variants in a Chinese patient with AS and to review the relevant literature. Genomic DNA extracted from a 10‑year‑old male with AS was evaluated using a disease‑ ...[more]

PMID: 32945434

Similar Datasets

Project description:PurposeAlström syndrome (AS) is a rare monogenic autosomal recessively inherited disorder characterized by cone rod dystrophy and multiple organ dysfunction. Mutations in the Alström syndrome 1 (ALMS1) gene have been found to be causative for AS. The purpose of this study was to identify ALMS1 mutations and to assess the clinical features of Chinese patients with AS.MethodsDetailed ocular and laboratory examinations were performed. Peripheral blood samples were collected from patients and their parents. Genomic DNA was extracted with a Qiagen kit. Exons and exon/intron junctions of ALMS1 were amplified with polymerase chain reaction (PCR) and screened for mutations with Sanger sequencing. The results were compared with the ALMS1 transcript to exclude polymorphisms and confirm pathogenic mutations.ResultsSeven patients from five unrelated non-consanguineous families were diagnosed with AS. All patients had cone rod dystrophy with impaired visual acuity, photophobia, and nystagmus. Other clinical features, including sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes mellitus, renal and hepatic dysfunction, hyperlipidemia, hypothyroidism, mental retardation, acanthosis nigricans, and scoliosis, were present. Sequencing revealed two novel mutations, p.N3150Kfs2X and p.V3154Xfs, in patient 1; one novel mutation, p.N3672Ifs11X, and one previously reported nonsense mutation, p.R3703X, in patient 2; novel mutations p.S2479X and p.R3611Efs7X in patient 3; one novel homozygous mutation, p.S695X, in patients 4 and 5; and two novel mutations, p.H688HfsX and p.Q3147Qfs2X, in patients 6 and 7. These mutations were not present in 100 unrelated healthy Chinese control subjects. The patients' parents were heterozygous carriers of the mutant allele.ConclusionsSeven Chinese patients with AS showed typical ophthalmic features and multiple organ dysfunction. Novel loss of function mutations in the ALMS1 gene are the underlying genetic defects.

Dataset Information

A novel variant in ALMS1 in a patient with Alstrom syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review.

Publications

A novel variant in ALMS1 in a patient with Alström syndrome and prenatal diagnosis for the fetus in the family: A case report and literature review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets