Basel-Vanagaite Lina, Pillar Nir, Isakov Ofer, Smirin-Yosef Pola, Lagovsky Irina, Orenstein Naama, Salmon-Divon Mali, Tamary Hannah, Zaft Tami, Bazak Lily, Meyerovitch Joseph, Pelli Tal, Botchan Shay, Farberov Luba, Weissglas-Volkov Daphna, Shomron Noam
Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Gene. 2017 Mar 30;606:47-52. doi: 10.1016/j.gene.2017.01.001. Epub 2017 Jan 9.
In this study, we report a family with X-linked recessive syndrome caused by mutated AMMECR1 and characterized by elliptocytosis with or without anemia, midface hypoplasia, proportionate short stature and hearing loss. Recently, mutations in AMMECR1 were reported in two maternal half-brothers, presenting with nephrocalcinosis, midface hypoplasia and, in one of the siblings, deafness and elliptocytosis. AMMECR1 gene is localized in the critical region of contiguous deletion syndrome on Xq22.3 implicated in Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis (AMME complex). Interestingly, alternative splicing of exon 2, the same exon harboring the truncating mutation, was observed in the proband and in his unaffected mother. Alternative splicing of this exon is predicted to lead to an in-frame deletion. We provide further evidence that mutated AMMECR1 gene is responsible for this clinically recognizable X-linked condition with variable expressivity.
在本研究中，我们报告了一个由AMMECR1基因突变引起的X连锁隐性综合征家系，其特征为伴有或不伴有贫血的椭圆形红细胞增多症、面中部发育不全、身材比例矮小和听力丧失。最近，在两个同父异母兄弟中报道了AMMECR1基因突变，他们表现为肾钙质沉着症、面中部发育不全，其中一个兄弟还伴有耳聋和椭圆形红细胞增多症。AMMECR1基因位于Xq22.3上与Alport综合征、智力发育迟缓、面中部发育不全和椭圆形红细胞增多症（AMME综合征）相关的连续性缺失综合征关键区域。有趣的是，在先证者及其未受影响的母亲中观察到外显子2的可变剪接，该外显子正是发生截短突变的外显子。预计该外显子的可变剪接会导致框内缺失。我们提供了进一步的证据，证明AMMECR1基因突变是导致这种具有可变表达性的临床可识别X连锁疾病的原因。
