Maltese Paolo E, Iarossi Giancarlo, Ziccardi Lucia, Colombo Leonardo, Buzzonetti Luca, Crinò Antonino, Tezzele Silvia, Bertelli Matteo
Magi's Lab, Rovereto, TN, Italy.
Department of Ophthalmology, Bambino Gesù IRCCS Children's Hospital, Rome, Italy.
Eur J Med Genet. 2018 Feb;61(2):79-83. doi: 10.1016/j.ejmg.2017.10.016. Epub 2017 Oct 24.
Obesity phenotype can be manifested as an isolated trait or accompanied by multisystem disorders as part of a syndromic picture. In both situations, same molecular pathways may be involved to different degrees. This evidence is stronger in syndromic obesity, in which phenotypes of different syndromes may overlap. In these cases, genetic testing can unequivocally provide a final diagnosis. Here we describe a patient who met the diagnostic criteria for Alström syndrome only during adolescence. Genetic testing was requested at 25 years of age for a final confirmation of the diagnosis. The genetic diagnosis of Alström syndrome was obtained through a Next Generation Sequencing genetic test approach using a custom-designed gene panel of 47 genes associated with syndromic and non-syndromic obesity. Genetic analysis revealed a novel homozygous frameshift variant p.(Arg1550Lysfs*10) on exon 8 of the ALMS1 gene. This case shows the need for a revision of the diagnostic criteria guidelines, as a consequence of the recent advent of massive parallel sequencing technology. Indications for genetic testing reported in these currently accepted diagnostic criteria for Alström syndrome, were drafted when sequencing was expensive and time consuming. Nowadays, Next Generation Sequencing testing could be considered as first line diagnostic tool not only for Alström syndrome but, more generally, for all those atypical or not clearly distinguishable cases of syndromic obesity, thus avoiding delayed diagnosis and treatments. Early diagnosis permits a better follow-up and pre-symptomatic interventions.
肥胖表型可表现为一种孤立的特征，或作为综合征表现的一部分伴有多系统疾病。在这两种情况下，相同的分子途径可能会不同程度地参与其中。在综合征性肥胖中，这种证据更为有力，不同综合征的表型可能会重叠。在这些病例中，基因检测能够明确地提供最终诊断。在此，我们描述一名仅在青春期符合阿尔斯特伦综合征诊断标准的患者。患者25岁时进行了基因检测以最终确诊。通过使用定制设计的包含47个与综合征性和非综合征性肥胖相关基因的基因panel的下一代测序基因检测方法，获得了阿尔斯特伦综合征的基因诊断。基因分析显示ALMS1基因第8外显子上有一个新的纯合移码变异p.(Arg1550Lysfs*10)。由于大规模平行测序技术的近期出现，该病例表明需要修订诊断标准指南。目前被接受的阿尔斯特伦综合征诊断标准中报告的基因检测指征，是在测序既昂贵又耗时的时候起草的。如今，下一代测序检测不仅可被视为阿尔斯特伦综合征的一线诊断工具，更普遍地说，对于所有那些综合征性肥胖的非典型或难以明确区分的病例，都可作为一线诊断工具，从而避免诊断和治疗的延迟。早期诊断有助于更好的随访和症状前干预。
