Titomanlio Luigi, Giurgea Irina, Baumann Clarisse, Elmaleh Monique, Sachs Philippe, Chalard François, Aboura Azzedine, Verloes Alain
Department of Child Neurology, AP-HP Robert Debré Hospital, Paris, France.
Eur J Hum Genet. 2006 Aug;14(8):971-4. doi: 10.1038/sj.ejhg.5201635. Epub 2006 May 17.
Partial absence of the sacrum is a rare congenital defect that also occurs as an autosomal-dominant trait, whereas imperforate/ectopic anus is a relatively common malformation, usually observed in multiple congenital anomalies syndromes. We report on a girl born to healthy consanguineous parents (first cousins once removed) with anal imperforation and associated rectovaginal fistula and partial sacral agenesis. Facial dysmorphism included a high forehead, epicanthic folds, downslanting palpebral fissures, hypertelorism and a depressed nasal root. Brain MRI showed a bilateral opercular dysplasia with a unilateral (right) pachygyria; MRI and X-ray imaging of the spine disclosed a tethered cord associated with partial sacral agenesis. She showed a moderate developmental delay. Ophthalmologic examination evidenced bilateral microphthalmos and relative microcornea. Cytogenetic studies in our patient disclosed a pure de novo 6q25.3 --> qter deletion. By genotype analysis, we detected in our patient a maternal allele loss encompassing D6S363 and D6S446. Pure distal 6q deletion is a rare anomaly, reported in association with sacral/anorectal malformations (sacral agenesis, anal imperforation/ectopia) and never with cortical dysplasia. Pooling deletion mapping information in patients with pure terminal and interstitial 6q deletion allowed us to define a critical region spanning 0.3 Mb between the markers D6S959 and D6S437 for sacral/anal malformations. We hypothesize that haploinsufficiency for a gene within the deleted region may impair normal development of caudal structures, possibly acting on the notochordal development. European Journal of Human Genetics (2006) 14, 971-974. doi:10.1038/sj.ejhg.5201635; published online 17 May 2006.
骶骨部分缺如是一种罕见的先天性缺陷，也作为常染色体显性性状出现，而肛门闭锁/异位肛门是一种相对常见的畸形，通常在多种先天性异常综合征中观察到。我们报告了一名健康近亲父母（隔一代的表亲）所生的女孩，她患有肛门闭锁并伴有直肠阴道瘘和部分骶骨发育不全。面部畸形包括高额、内眦赘皮、睑裂向下倾斜、眼距增宽和鼻根凹陷。脑部磁共振成像（MRI）显示双侧岛盖发育异常并伴有单侧（右侧）巨脑回；脊柱的MRI和X线成像显示存在与部分骶骨发育不全相关的脊髓栓系。她有中度发育迟缓。眼科检查证实双侧小眼畸形和相对小角膜。对我们的患者进行的细胞遗传学研究发现了一个纯合的新发6q25.3→qter缺失。通过基因型分析，我们在患者中检测到包含D6S363和D6S446的母源等位基因缺失。纯合的6q远端缺失是一种罕见的异常，与骶骨/肛门直肠畸形（骶骨发育不全、肛门闭锁/异位）相关报道过，但从未与皮质发育异常相关。汇总纯合的末端和中间6q缺失患者的缺失定位信息，使我们能够确定一个跨越0.3 Mb、位于标记D6S959和D6S437之间的关键区域，该区域与骶骨/肛门畸形相关。我们推测，缺失区域内一个基因的单倍剂量不足可能会损害尾端结构的正常发育，可能作用于脊索发育。《欧洲人类遗传学杂志》（2006年）14卷，971 - 974页。doi:10.1038/sj.ejhg.5201635；2006年5月17日在线发表。
