■连接粘附分子3(JAM3/JAM-C;OMIM#606871)的致病变体是罕见的隐性疾病的原因,称为大脑出血性破坏,室管膜下钙化,和白内障(HDBSCC,OMIM#613730)疾病。类似的表型是普遍的,包括先天性白内障和脑出血,在生命的最初几周死亡率很高,幸存者的神经系统预后较差。我们旨在描述和启发新患者的新表型和基因型,并回顾全球所有报告患者的文献。
■我们报告了一个新患者的产前和产后表型的病例,该患者在JAM3中具有一种新的致病性功能丧失变异,其产前出现白内障和脑异常,产后出现脑出血,未能茁壮成长(FTT),进行性小头畸形,复发性后囊混浊,和听觉神经病。
■这项研究启发了JAM3在大脑正常发育中的新功能,眼透镜,听觉系统,可能还有胃肠道.这项研究是首次报道早在妊娠23周就出现明显的白内障,尽管进行了复发性后囊切除术和前路玻璃体切除术,但复发性后囊混浊的罕见现象。我们认为听觉神经病,这是第一次在这里报道,是HDBSCC表型的一部分,可能是由于外周第八神经的内皮微血管破坏,或者可能是由于突触到脑干的神经传导受损。
■产前白内障,大脑异常,FTT,和听觉神经病是HDBSCC疾病表型的一部分。我们建议将JAM3纳入已知导致先天性白内障的基因列表中,脑出血,和听力损失。进一步的研究应解决敲除小鼠模型中的听觉神经病和FTT现象。我们进一步建议进行全面的眼科,听力学,以及对全世界存活患者的胃肠病学评估,以进一步证实这种罕见实体中的这些新现象。
UNASSIGNED: Pathogenic variants of the junctional adhesion molecule 3 (JAM3/JAM-C; OMIM#606871) is the cause of the rare recessive disorder called hemorrhagic destruction of the brain, subependymal calcification, and cataracts (HDBSCC, OMIM#613730) disease. A similar phenotype is universal, including congenital cataracts and brain hemorrhages with high mortality rate in the first few weeks of life and with a poor neurologic outcome in survivors. We aim to describe and enlighten novel phenotype and genotype of a new patient and review the literature regarding all reported patients worldwide.
UNASSIGNED: We report the case of a prenatal and postnatal phenotype of a new patient with a novel pathogenic loss-of-function variant in JAM3, who presented prenatally with cataracts and brain anomalies and postnatally with brain hemorrhages, failure to thrive (FTT), progressive microcephaly, recurrent posterior capsule opacities, and auditory neuropathy.
UNASSIGNED: This study enlightens novel possible functions of JAM3 in the normal development of the brain, the ocular lenses, the auditory system, and possibly the gastrointestinal tract. This study is the first to report of cataracts evident in as early as 23 weeks of gestation and a rare phenomenon of recurrent posterior capsule opacities despite performing recurrent posterior capsulectomy and anterior vitrectomy. We suggest that auditory neuropathy, which is reported here for the first time, is part of the phenotype of HDBSCC, probably due to an endothelial microvasculature disruption of the peripheral eighth nerve or possibly due to impaired nerve conduction from the synapse to the brainstem.
UNASSIGNED: Prenatal cataracts, brain anomalies, FTT, and auditory neuropathy are part of the phenotype of the HDBSCC disease. We suggest including JAM3 in the gene list known to cause congenital cataracts, brain hemorrhages, and hearing loss. Further studies should address the auditory neuropathy and FTT phenomena in knockout mice models. We further suggest performing comprehensive ophthalmic, audiologic, and gastroenterologic evaluations for living patients worldwide to further confirm these novel phenomena in this rare entity.