کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2813850 1569476 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B-related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes
چکیده انگلیسی

Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C-terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medical Genetics - Volume 58, Issue 10, October 2015, Pages 550–555
نویسندگان
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