Genetic evaluation of patients with Alström syndrome in the Polish population.
Alström syndrome (AS) is a rare syndromic form of obesity and type 2 diabetes (T2D) in children coexisting with retinal dystrophy and disorders of many organs caused by the mutations in ALMS1 gene. Aim of this study was to identify the causative mutations in ALMS1 in a group of 12 patients of Polish origin with clinical symptoms of AS, and their 21 first-degree relatives. Using DNA sequencing, nine different mutations including three novel were identified. These mutations were not present in 212 Polish individuals with no symptoms of AS, subjected to whole-exome sequencing and collected in a national registry. Looking for genotype-phenotype relationships, we confirmed a severe phenotype in a boy with homozygous mutation in exon 16, and a relationship between a presence of T2D and mutations in exon 19. Evaluation of the type of mutation and its clinical effects gives hope for earlier diagnosis of AS in future patients and more advanced therapeutic approaches for patients with already diagnosed AS.
Department of Pediatrics, Oncology, Hematology and Diabetology, Lodz, Poland.
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A
Zmyslowska
Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland.
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M
Borowiec
Department of Clinical Genetics, Medical University of Lodz, Lodz, Poland.
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K
Antosik
Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
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R
Ploski
Department of Endocrinology for Children and Adolescents, Jagiellonian University, Cracow, Poland.
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M
Ciechanowska
Department of Pediatrics, Endocrinology and Neurology, Children's hospital, Torun, Poland.
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B
Iwaniszewska
Outpatient Genetic Clinic, Bialystok, Poland.
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A
Jakubiuk-Tomaszuk
Department of Gastroenterology, Hepatology, Nutrition Disorders and Pediatrics, Warsaw, Poland.
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W
Janczyk
Department of Clinical Genetics, Medical University of Poznan, Poznan, Poland.
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M
Krawczynski
Department of Pediatric Endocrinology, Wroclaw Medical University, Wroclaw, Poland.
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B
Salmonowicz
Department of Endocrinology for Children and Adolescents, Jagiellonian University, Cracow, Poland.
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M
Stelmach
Department of Pediatrics, Oncology, Hematology and Diabetology, Lodz, Poland.
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W
Mlynarski
ALMS1 gene; Alström syndrome; monogenic diabetes; novel mutations