Tosca Lucie, Brisset Sophie, Petit François M, Metay Corinne, Latour Stéphanie, Lautier Benoît, Lebas Axel, Druart Luc, Picone Olivier, Mas Anne-Elisabeth, Prévot Sophie, Tardieu Marc, Goossens Michel, Tachdjian Gérard
AP-HP, Histologie-Embryologie-Cytogénétique, Hôpital Antoine Béclère, France.
Eur J Med Genet. 2011 Sep-Oct;54(5):e489-94. doi: 10.1016/j.ejmg.2011.06.004. Epub 2011 Jun 21.
Pure interstitial deletions of the long arm of chromosome 13 are correlated with variable phenotypes according to the size and the location of the deleted region. Deletions involving the 13q13q21 region are rare. In order to establish interstitial 13q genotype-phenotype correlation, we used high resolution 244K oligonucleotide array in addition to conventional karyotype and molecular (fluorescent in situ hybridization, microsatellite markers analysis) techniques in two independent probands carrying a deletion 13q13 to 13q21. First patient was a 3-year-old girl with mental retardation and dysmorphy carrying a 13q13.3q21.31 de novo deletion diagnosed post-natally. The second one was a fetus with de novo del(13)(q14q21.2) associated with first trimester increased nuchal translucency. We showed that specific dysmorphic features (macrocephaly, high forehead, hypertelorism, large nose, large and malformed ears and retrognathia) were correlated to the common 13q14q21 chromosomal segment. Physical examination revealed overgrowth with global measurement up to the 95th percentile in both probands. This is the second description of overgrowth in patients carrying a 13q deletion. Haploinsufficiency of common candidates genes such as CKAP2, SUGT1, LECT1, DCLK1 and SMAD9, involved in cell division and bone development, is a possible mechanism that could explain overgrowth in both patients. This study underlines also that cytogenetic analysis could be performed in patients with overgrowth.
13号染色体长臂的单纯间质缺失与缺失区域的大小和位置相关的可变表型有关。涉及13q13q21区域的缺失很少见。为了建立间质13q基因型与表型的相关性，我们在两名携带13q13至13q21缺失的独立先证者中，除了使用传统核型分析和分子（荧光原位杂交、微卫星标记分析）技术外，还使用了高分辨率244K寡核苷酸阵列。首例患者是一名3岁智力发育迟缓且有畸形的女孩，出生后诊断为13q13.3q21.31新发缺失。第二例是一名胎儿，新发del(13)(q14q21.2)，与孕早期颈部半透明厚度增加有关。我们发现特定的畸形特征（巨头畸形、高额、眼距过宽、大鼻子、大耳且畸形以及下颌后缩）与常见的13q14q21染色体片段相关。体格检查显示两名先证者均有生长过度，总体测量值高达第95百分位。这是对携带13q缺失患者生长过度的第二次描述。参与细胞分裂和骨骼发育的常见候选基因如CKAP2、SUGT1、LECT1、DCLK1和SMAD9的单倍剂量不足，可能是解释两名患者生长过度的一种机制。这项研究还强调，对于生长过度的患者可以进行细胞遗传学分析。
