title: Long-term clinical follow-up and molecular testing for diagnosis of the first Tunisian family with Alström syndrome.
abstract: Alström syndrome is a clinically complex disorder characterized by progressive degeneration of sensory functions, resulting in visual and audiological impairment as well as metabolic disturbances. It is caused by recessively inherited mutations in the ALMS1 gene, which codes for a centrosomal/basal body protein. The purpose of this study was to investigate the genetic and clinical features of two Tunisian affected siblings with Alström syndrome. Detailed clinical examinations were performed including complete ophthalmic examination, serial audiograms and several biochemical and hormonal blood tests. For the molecular study, first genomic DNA was isolated using a standard protocol. Then, linkage analysis with microsatellite markers was performed and DNA array was used to detect known mutations. Subsequently, all ALMS1 exons were simultaneously sequenced for one affected patient with the TaGSCAN targeted sequencing panel. Finally, segregation of the causal variant was performed by Sanger sequencing. Both affected siblings had cone rod dystrophy with impaired visual acuity, sensorineural hearing loss and truncal obesity. One affected individual showed insulin resistance without diabetes mellitus. Other clinical features including cardiac and pulmonary dysfunction, hypothyroidism, hyperlipidemia, acanthosis nigricans, renal and hepatic dysfunction were absent. Genetic analysis showed the presence of a homozygous splice site mutation (c.10388-2A > G) in both affected siblings. Although Alström syndrome is relatively well characterized disease, this syndrome is probably misdiagnosed in Tunisia. Here, we describe the first report of Tunisian patients affected by this syndrome and carrying a homozygous ALMS1 mutation. The diagnosis was suspected after long-term clinical follow-up and confirmed by genetic testing.
authors: Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, Tunisia; Department of Otorhinolaryngology, Habib Bourguiba Teaching Hospital, University of Sfax, Tunisia. Electronic address: amine.chakroun22@gmail.com.
authors: Amine
authors: A
authors: Chakroun
authors: Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, Tunisia.
authors: Mariem
authors: M
authors: Ben Said
authors: Department of Ophthalmology, Habib Bourguiba Teaching Hospital, University of Sfax, Tunisia.
authors: Amine
authors: A
authors: Ennouri
authors: Department of Otorhinolaryngology, Habib Bourguiba Teaching Hospital, University of Sfax, Tunisia.
authors: Imen
authors: I
authors: Achour
authors: Department of Endocrinology, Hedi Chaker Teaching Hospital, University of Sfax, Tunisia.
authors: Mouna
authors: M
authors: Mnif
authors: Department of Endocrinology, Hedi Chaker Teaching Hospital, University of Sfax, Tunisia.
authors: Mohamed
authors: M
authors: Abid
authors: Department of Otorhinolaryngology, Habib Bourguiba Teaching Hospital, University of Sfax, Tunisia.
authors: Abdelmonem
authors: A
authors: Ghorbel
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Jan D
authors: JD
authors: Marshall
authors: The Jackson Laboratory, Bar Harbor, ME, USA.
authors: Jürgen K
authors: JK
authors: Naggert
authors: Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, Tunisia.
authors: Saber
authors: S
authors: Masmoudi
mesh_terms: D000293:Adolescent; D000328:Adult; D056769:Alstrom Syndrome / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D014416:Tunisia
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins
keywords: ALMS1; Alström syndrome; DNA sequencing; Microarray analysis; Mutation