Fernández-Hernández Liliana, Navarro-Cobos María José, Alcántara-Ortigoza Miguel Angel, Ramos-Ángeles Sandra Elena, Molina-Álvarez Bertha, Díaz-Cuéllar Sinhué, Asch-Daich Bárbara, González-Del Angel Ariadna
1Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Ciudad de México, México.
Centro de Cirugía Especial de México, Institución de Asistencia Privada, Ciudad de México, México.
Mol Cytogenet. 2019 Aug 1;12:35. doi: 10.1186/s13039-019-0438-0. eCollection 2019.
The 17p11.2p12 locus is an unstable region that is predisposed to several known genomic disorders and non-recurrent rearrangements that yield varied and wide-ranging phenotypes. Nearly 1% of male newborns have deletions in the Y chromosome; these events primarily involve the heterochromatic region, but may extend to euchromatic Yq segments containing azoospermia factor regions.
We describe the occurrence of two independent chromosomal rearrangements that originated as de novo events in a single male patient: a 10.8-Mb duplication of 17p11.2p12 and a 14.7-Mb deletion of Yq11. This individual shares some clinical characteristics with previously described patients having one or the other of these rearrangements, including global developmental delay, short stature, hypotonia, delayed puberty, certain facial features and a generalized demyelinating sensory-motor polyneuropathy without clinical manifestation. Our patient also presents some features that were not previously described in relevant individuals, including camptodactyly, preauricular pits and hypertrichosis of the back and elbows.
To our knowledge, this is the first patient to be reported with independent de novo deletion/duplication events involving chromosomes 17 and Y. We discuss possible responsible mechanisms and address the phenotype, particularly in light of the clinical features that were not previously reported for patients bearing a duplication of 17p11.2p12 or a deletion of Yq11. We suggest that some of the previously reported patients with Yq11 deletion and clinical manifestations other than male infertility may have additional chromosomal imbalances that could be identified by chromosome microarray analysis, as illustrated by the present case.
17p11.2p12基因座是一个不稳定区域，易发生多种已知的基因组疾病和非重复性重排，从而产生多样且广泛的表型。近1%的男性新生儿存在Y染色体缺失；这些事件主要涉及异染色质区域，但可能延伸至包含无精子症因子区域的常染色质Yq片段。
我们描述了在一名男性患者中发生的两个独立的染色体重排，它们均为新生事件：17p11.2p12区域10.8 Mb的重复和Yq11区域14.7 Mb的缺失。该个体与先前描述的具有上述其中一种重排的患者有一些共同临床特征，包括全面发育迟缓、身材矮小、肌张力减退、青春期延迟、某些面部特征以及无临床表现的全身性脱髓鞘感觉运动性多神经病。我们的患者还呈现出一些先前在相关个体中未描述的特征，包括手指弯曲畸形、耳前凹以及背部和肘部多毛症。
据我们所知，这是首例被报道的涉及17号和Y染色体独立新生缺失/重复事件的患者。我们讨论了可能的致病机制，并阐述了该患者的表型，特别是鉴于先前未报道过携带17p11.2p12重复或Yq11缺失的患者具有这些临床特征。我们认为，如本病例所示，一些先前报道的具有Yq11缺失且除男性不育外还有临床表现的患者可能存在其他染色体失衡，可通过染色体微阵列分析来识别。
