Genesio Rita, Ronga Valentina, Castelluccio Pia, Fioretti Gennaro, Mormile Angela, Leone Graziella, Conti Anna, Cavaliere Maria Luigia, Nitsch Lucio
DMMBM, Universita' di Napoli Federico II, Naples, Italy.
UOSC Genetica Medica, AORN A. Cardarelli, Naples, Italy.
Mol Cytogenet. 2013 Aug 1;6(1):29. doi: 10.1186/1755-8166-6-29.
Partial monosomies of chromosome 16q are rare and overlapping effects from complex chromosomal rearrangements often hamper genotype-phenotype correlations for such imbalances. Here, we report the clinical features of an isolated partial monosomy 16q21q22.1 in a boy with a complex de novo rearrangement possibly resulting from a chromothripsis event.
The patient presented with low birth weight, microcephaly, developmental delay, facial dysmorphisms, short stature, dysmorphic ears and cardiopathy. Standard and molecular cytogenetics showed a complex rearrangement characterised by a pericentromeric inversion in one of chromosomes 12 and an inverted insertional translocation of the 12q14q21.1 region, from the rearranged chromosome 12, into the q21q22.1 tract of a chromosome 16. Array-CGH analysis unravelled a partial 16q21q22.1 monosomy, localised in the rearranged chromosome 16.
The comparison of the present case to other 16q21q22 monosomies contributed to narrow down the critical region for cardiac anomalies in the 16q22 deletion syndrome. However, more cases, well characterised both for phenotypic signs and genomic details, are needed to further restrict candidate regions for phenotypic signs in 16q deletions. The present case also provided evidence that a very complex rearrangement, possibly caused by a chromothripsis event, might be hidden behind a classical phenotype that is specific for a syndrome.
16号染色体长臂部分单体异常较为罕见，复杂染色体重排产生的重叠效应常常妨碍此类染色体失衡的基因型与表型之间的关联。在此，我们报告一名患有孤立性16q21q22.1部分单体异常的男孩的临床特征，该异常可能源于一次染色体碎裂事件导致的复杂新发重排。
该患者表现为低出生体重、小头畸形、发育迟缓、面部畸形、身材矮小、耳部畸形和心脏病。标准和分子细胞遗传学显示存在一种复杂重排，其特征为12号染色体中的一条发生着丝粒周围倒位，以及12q14q21.1区域从重排后的12号染色体发生反向插入易位至16号染色体的q21q22.1区段。阵列比较基因组杂交（Array-CGH）分析揭示了位于重排后的16号染色体上的16q21q22.1部分单体异常。
将本病例与其他16q21q22单体异常病例进行比较，有助于缩小16q22缺失综合征中心脏异常的关键区域。然而，需要更多在表型特征和基因组细节方面都有充分表征的病例，以进一步限定16q缺失中表型特征的候选区域。本病例还提供了证据，表明一个可能由染色体碎裂事件导致的非常复杂的重排，可能隐藏在一种综合征特有的经典表型背后。
