High-Resolution Array Comparative Genomic Hybridization Utility in Polish Newborns with Isolated Cleft Lip and Palate

Abstract

Cleft lip with or without cleft palate is one of the most common birth defects of unknown etiology. A fraction of its genetic causes is attributable to copy number variations detected by array comparative genomic hybridization. The value of array comparative genomic hybridization screening as a first-tier test in the newborn population with multiple congenital anomalies has now been accepted. Due to unspecific clinical picture at this age, it can also be applied to neonates with isolated anomalies. Our purpose was to assess utility of array comparative genomic hybridization in the population of newborns with isolated cleft lip and palate. We conducted the study in a group of 52 Polish newborns with apparently isolated cleft lip and palate. In the study group, we found 8 rearrangements. Of these, 2 de novo events have been noted that potentially explain the phenotype. In addition, 2 novel candidate genes for cleft lip and palate, CHN2 and CDH19, are suggested. Given the high number of inherited potentially benign changes, we question the clinical utility of array comparative genomic hybridization in the newborn population with isolated cleft lip and palate, at the same time pointing to the need of skilled professional's clinical assessment at a later age. However, the value of this technology in searching for the cause of isolated anomalies cannot be underestimated.

Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans

“…The third positively selected protease gene from the intestine is the serine proteinase, TMPRSS15 (also known as PRSS7 ) encoding enterokinase, that activates trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases (Imamura and Kitamoto 2003). Functional analysis of the TMPRSS15 variants showed enterokinase deficiency, and cause a malabsorption disorder characterized by diarrhea and failure to thrive (Szczałuba et al 2015). When we mapped these positively selected residues onto the three-dimensional crystal structure of these genes, it was found CTRC (T5S) and PRSS1 (A13V) each had a positively selected site located on the signal peptide (supplementary table S4, Supplementary Material online), which directs the protein to the endoplasmic reticulum and associated with the secretion of the mature peptide (Király et al 2007).…”

Identification of genomic imbalances in oral clefts

“…In fact, only ten articles reporting a series of OC using CMA were identified up to November 2019. 4 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 …”

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

“…The advent of technologies that allowed whole-genome analysis like CMA and NGS and its inclusion into medical practice has contributed to the identification of genetic causes related to CA. Association between pathogenic CNVs in patients presenting MCA and non-syndromic CA has been largely described [ 7 , 13 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ], although only a few large cohort studies have been specifically performed aiming at analyzing the whole genome by array-CGH in samples with birth defects in Latin American populations [ 93 ]. Similarly, NGS data from patients with CA from our region is still scarcely represented in most of the clinical databases worldwide or in the literature [ 98 , 99 ].…”