Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
Authors: Yifeng Yang
Yi Yin
Zhiping Tan
Xicheng Deng
Guangxian Yang
Jian Liu
Journal: BMC medical genomics (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hearing loss; PTPRQ mutation; SALL1 mutation; Townes-brocks syndrome.
Affiliations: Department of Cardiothoracic Surgery, Hunan Children's Hospital, No. 86 Ziyuan Road, Changsha, Hunan Province, 410007, China. ., Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China., Department of Cardiothoracic Surgery, Hunan Children's Hospital, No. 86 Ziyuan Road, Changsha, Hunan Province, 410007, China.

Abstract:  Background: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband's father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband's mother presented nonsyndromic hearing loss, and the proband's mother's parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband's mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss. 

Retracted: No

PubPeer comments:
 Figure 1A. * Red arrows: two panels appear to show an overlap if one of them is rotated 180 degrees. ![file] , 
 Figure 4B and 5D. * Cyan boxes: Two panels that appear to represent different experiments look similar. ![file] , 
 Figure 5C. * Blue boxes: the Sorafenib + DZNep panels for both cell lines appear to show an overlap. ![file] ,