Novel de novo interstitial deletion in 2q36.1q36.3 causes syndromic hearing loss and further delineation of the 2q36 deletion syndrome

Abstract

Background: Deletions of the interstitial 2q36 are uncommon and associated with varying phenotypes. However, the list of currently known phenotypes is still far complete for an understanding of the interstitial 2q36 deletion syndrome characteristics.

Aims/Objectives: To identify the genetic and clinical characterization of a 6-year-old male patient suffering from a severe form of syndromic hearing loss, with brachydactyly family history.

Material and Methods: We performed conventional cytogenetic analysis on the peripheral blood lymphocytes and whole exome sequencing and SNP array analysis on DNA samples from the family.

Results: The proband showed signs such as bilateral sensorineural deafness, ocular hypertelorism, flat facial profile and several decayed teeth, slightly ulnar deviation of the hands, single transverse palmar crease, short stature and intellectual disability. Through cytogenetic and molecular genetic analysis, we discovered that the syndromic hearing loss was the result of a de novo 5.175-Mb microdeletion at chromosome 2q36.1q36.3 whose breakpoints had been precisely mapped by us.

Conclusions and Significance: Our study warns that auditory assessment should be evaluated even if the patient with 2q36 deletion syndrome is not obviously presenting hearing loss. In addition, a comprehensive molecular genetics diagnosis involving multiple methods is important to support accurate genetic characterization of this syndrome.

背景：间质2q36的缺失并不常见。它与不同的表型相关。然而, 对于理解间质2q36缺失综合征的特征, 目前已知的表型列名仍然很不完整。

目的：为一位有短指家族病史的患有严重的综合征性听力损失的6岁男性患者, 确定遗传和临床特征。

材料与方法：对外周血淋巴细胞进行常规细胞遗传学分析, 对家族DNA样本进行全外显子测序和单核苷酸多态性阵列分析。

结果：先证者表现出诸如双侧感音神经性耳聋、眼压增高、面部扁平、多颗龋齿、手稍偏向尺骨、手掌单横纹、身材矮小、智力障碍等症状。通过细胞遗传学和分子遗传学分析, 我们发现综合征性听力损失是2q36.1q36.3号染色体新出现5.175-Mb微缺失的结果, 其断裂点已被我们精确定位。

结论和意义：我们的研究警告, 即使2q36缺失综合征患者没有明显的听力损失, 也应进行听力评估。此外, 涉及多种方法的综合性分子遗传学诊断对于支持该综合征的准确遗传特征具有重要意义。

Keywords:

• Syndromic hearing loss
• microdeletion
• 2q36.1-2q36.3
• brachydactyly

Acknowledgements

The authors thank the family for their invaluable cooperation and participation.

Disclosure statement

The authors declare that they have no competing interests. Conceived and designed the experiments: QW JG. Performed the experiments: JG, LY and HW. Analyzed the data: JG and LY. Contributed reagents/materials/analysis tools: HW, JY, GC, CZ and DW. Wrote the paper: JG and QW. Critically read and discussed the manuscript: JG, LY, DW and QW. All authors read and approved the final manuscript. We obtained written informed consent for publishing all data of this study from all the participants, such as medical data, images and genetic results. Written informed consent was obtained from the next of kin on the behalf of the minors/children who participants involved in this study.

Additional information

Funding

This work was supported by National Key Basic Research Program of China [2014CB943001] and National Natural Science Foundation of China [81530032, 81830028].