Bardet-Biedl综合征(BBS)是一种以杆锥营养不良为特征的多系统疾病,躯干肥胖,后轴多指,认知障碍,男性低促性腺激素性性腺功能减退,复杂的女性泌尿生殖系统畸形,和肾脏异常。在BBS中存在很大的临床和遗传异质性。这里,我们报告一个多指的病人,高回声肾的大小随着正常的皮质髓质分化而增加,肛门闭锁,和生殖器畸形,存在生殖器结节和腹侧尿道口,伴有两个未融合的外侧生殖器肿胀和尿道褶皱缺失,在46,XY核型的背景下。
进行核型和单个外显子组测序以寻找我们患者中描述的特征的遗传病因。
我们确定了BBS4基因中外显子4至6的纯合框内缺失(NM-033028(BBS4-i001):c。[(157-?)_(405?)del]p。(Ala53-Trp135del),被归类为致病变异。该分析允许在该患者中进行BBS类型4的分子诊断。
复杂的生殖器畸形仅在女性BBS6患者中报道,男性BBS4患者迄今未报告生殖器异常和肛门闭锁。我们讨论了这种表型的可能假设,包括纤毛病之间的表型重叠。
Bardet-Biedl syndrome (BBS) is a multisystemic disorder characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. There is a large clinical and also genetic heterogeneity in BBS. Here, we report a patient with polydactyly, hyperechogenic kidneys increased in size with normal corticomedullary differentiation, anal imperforation, and malformation of genitals with presence of a genital tubercle with ventral urethral meatus associated with two unfused lateral genital swelling and absent urethral folds, in the context of 46, XY karyotype.
Karyotype and solo exome sequencing were performed to look for a genetic etiology for the features described in our patient.
We identified a homozygous in-frame deletion of exons 4 to 6 in the BBS4 gene (NM-033028 (BBS4-i001): c.[(157-?)_(405 +?)del] p.(Ala53-Trp135del), which is classified as pathogenic variant. This analysis allowed the molecular diagnosis of BBS type 4 in this patient.
Complex genital malformations are only reported in female BBS6 patients yet, and genital abnormalities and anal imperforation are not reported in male BBS4 patients to date. We discuss the possible hypotheses for this phenotype, including the phenotypic overlap between ciliopathies.