伴有正常GGT的进行性家族性肝内胆汁淤积症的临床和遗传谱:31例儿科患者和16例新变体

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Nehal M Elkoofy, Mortada H El-Shabrawi, Mohamed A Elmonem
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引用次数: 0

摘要

进行性家族性肝内胆汁淤积综合征是一种罕见的常染色体隐性遗传病。我们提出了非洲人群中具有正常γ -谷氨酰转移酶(GGT)[正常GGT/PFIC]的PFIC儿童的第一个详细表型-基因型。31例儿童患者属于28个无血缘关系的埃及家庭,GGT/PFIC正常。系统分析临床、生化、组织病理学和遗传数据。患者男15例,女16例(确诊时55±52个月)。除胆汁淤积外,临床表现包括严重瘙痒(视觉模拟评分7.5±3.4)、肝肿大(80.6%)、睡眠不足(41.9%)、脾肿大(19.4%)。13/28个家族有ABCB11变异(PFIC2), 6/28个家族有ATP8B1 (PFIC1)和TJP2 (PFIC4)变异,2/28个家族有MYO5B变异(PFIC10), 1个家族有USP53变异(PFIC7)。报告了25种致病变异,包括16种新变异。与其他PFIC综合征相比,PFIC1患者受影响更严重,因为生长迟缓、兄弟姐妹死亡、皮肤变化和进展为胆道分流的发生率均显著高于PFIC1患者(p值分别为0.006、0.012、0.037和0.012)。相比之下,13名PFIC2患儿中没有一名进展为胆道分流,所有4名PFIC10患儿的肝脏转氨酶正常。我们的研究扩展了正常GGT/PFIC的全球表型和基因型知识,并将促进埃及对该综合征的更好护理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical and Genetic Spectra of Progressive Familial Intrahepatic Cholestasis With Normal GGT: 31 Pediatric Patients and 16 Novel Variants.

Progressive familial intrahepatic cholestasis (PFIC) syndromes are rare autosomal recessive disorders. We present the first detailed phenotype-genotype of PFIC children with normal gamma-glutamyltransferase (GGT) [normal GGT/PFIC] in an African population. Thirty-one pediatric patients belonging to 28 unrelated Egyptian families with normal GGT/PFIC were reported. Clinical, biochemical, histopathological, and genetic data were systematically analyzed. Patients were 15 males/16 females (55 ± 52 months at diagnosis). Apart from cholestasis, clinical features included severe pruritus (visual analogue scale 7.5 ± 3.4), hepatomegaly (80.6%), sleep deprivation (41.9%), and splenomegaly (19.4%). 13/28 families had ABCB11 variants (PFIC2), 6/28 families had ATP8B1 (PFIC1) and TJP2 (PFIC4) variants each, 2/28 had MYO5B variants (PFIC10), and one family had USP53 variants (PFIC7). Twenty-five disease-causing variants were reported, including 16 novel variants. PFIC1 patients were more severely affected compared to other PFIC syndromes, as the incidence of growth retardation, sibling deaths, skin changes, and progression to biliary diversion were all significantly higher (p value 0.006, 0.012, 0.037, and 0.012, respectively). In contrast, none of the 13 PFIC2 children progressed to biliary diversion, and all four PFIC10 children had normal liver transaminases. Our study expands the global phenotypic and genotypic knowledge of normal GGT/PFIC and will facilitate better care for the syndrome in Egypt.

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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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