Dataset Information

A novel variant site of Alstrom syndrome in a Chinese child: a case report.

ABSTRACT:

Background

Alstrom syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive inheritance of the ALMS1 gene. It manifests as multisystem dysfunction, displaying unique clinical signs and symptoms and various severity, which may lead to delayed prognosis or misdiagnosis in medical practice. Although almost 300 pathogenic variants have been reported, there are some variant sites that have not been recognized yet.

Case description

We report a case of a 14-year-old boy with manifestations, including binocular vision loss, acanthosis nigricans, type 2 diabetes, insulin resistance, elevated transaminase, hepatic fibrosis, and proteinuria. Compound heterozygous variants in the ALMS1 gene have been discovered by whole exon sequencing. One of his variant sites was C. 8158C>T, which was from his father. And the other variant site was C. 3575C>A, which was from his mother. To the great of our knowledge, this site has not been reported before. Both of the variants make the synthesis of the peptide chain terminated in advance and an incomplete polypeptide chain is formed.

Conclusions

The clinical presentations of ALMS are complicated and varied. Although early diagnosis can be made according to typical clinical symptoms, whole exon sequencing is necessary for the diagnosis of ALMS, as indicated by our study.

SUBMITTER: Xu R

PROVIDER: S-EPMC9085953 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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A novel variant site of Alstrom syndrome in a Chinese child: a case report.

Xu Rongrong R Zhou Hua H Fang Feng F Qiu Liru L Liu Xinglou X

Translational pediatrics 20220401 4

<h4>Background</h4>Alstrom syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive inheritance of the ALMS1 gene. It manifests as multisystem dysfunction, displaying unique clinical signs and symptoms and various severity, which may lead to delayed prognosis or misdiagnosis in medical practice. Although almost 300 pathogenic variants have been reported, there are some variant sites that have not been recognized yet.<h4>Case description</h4>We report a case of ...[more]

PMID: 35558973

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Project description:BackgroundAlström syndrome (AS) is a rare autosomal recessive disorder that leads to multiple organ fibrosis and failure. Precise diagnosis from the clinical symptoms is challenging due to its highly variabilities and its frequent confusion with other ciliopathies and genetic diseases. Currently, mutations in the ALMS1 gene have been reported as a major cause of AS, thus, it is crucial to focus on the detection and discovery of ALMS1 mutations.Case presentationWe present a case of a 13-year-old Chinese boy weighing 70 kg and standing 168 cm tall. He has two younger brothers. Their parents hail from different ancestral homes in eastern and northern China. The patient's primary clinical findings included visual impairment at the age of four and progressive hearing loss starting at the age of ten. Subsequently, at the age of twelve, the patient developed hyperlipidaemia and hyperinsulinemia. Ultrasonographic findings indicated the presence of gallstones and mild fatty liver. His Body Mass Index (BMI) significantly increased to 25 kg/m2 (ref: 18.5-23.9 kg/m2). Additionally, echocardiography revealed mild mitral and tricuspid regurgitation. Ultimately, Whole Exome Sequencing (WES) identified a new missense mutation in the ALMS1 gene (NG_011690.1 (NM_015120): c.9536G > A (p.R3179Q)). This missense mutation generated an aberrant splicer and disrupted the stability and hydrophobicity of proteins, which preliminarily determined as " likely pathogenic". Therefore, considering all the above symptoms and molecular analysis, we deduced that the patient was diagnosed with AS according to the guidelines. We recommended that he continue wearing glasses and undergo an annual physical examination.ConclusionIn this case report, we report a novel homozygous ALMS1 mutation associated with AS in the Chinese population, which expands the mutation spectrum of ALMS1. Genetic testing indeed should be incorporated into the diagnosis of syndromic deafness, as it can help avoid misdiagnoses of AS. While there is no specific treatment for AS, early diagnosis and intervention can alleviate the progression of some symptoms and improve patients' quality of life.

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 site of Alstrom syndrome in a Chinese child: a case report.

Background

Case description

Conclusions

Publications

A novel variant site of Alstrom syndrome in a Chinese child: a case report.

Similar Datasets

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