Molecular studies of segmental aneusomy: FISHing for the atypical cry in del(5)(p15.3)

Abstract

We report a newborn male with multiple congenital anomalies including growth retardation, hypotonia, dysmorphic facies, widely-spaced nipples, micropenis, cryptorchidism, optic nerve hypoplasia, heart disease, and a striking, high-pitched cry. Chromosome analysis revealed de novo partial trisomy 11q due to a der(5)t(5;11)(p15.3;q22). Fluorescence in situ hybridization (FISH) showed loss of the 5p telomere signal on the der(5) chromosome, indicating the infant has partial monosomy 5p in addition to partial trisomy 11q. Among cases involving trisomy 11q, an unusual cry has only been documented in the presence of a der(5)t(5p;11q). This apparent dependence of the abnormal cry on monosomy 5p suggested the same genetic mechanism that occurs in Cri du chat syndrome (CDCS) may be responsible for the atypical cry in der(5)t(5p;11q) individuals. Neither a commercial CDCS probe (LSI D5S23, D5S721) nor a series of BAC clones encompassing distal regions implicated in the CDCS-associated cat-cry were deleted in our patient. These results suggest a second cry-modifying locus maps telomeric to BAC RP11-94J21 in band 5p15.33. This locus may not only cause the abnormal cry in individuals with a der(5)t(5p;11q) but could also contribute to the phenotypic variability and discordant mapping studies observed for CDCS.

Large distal 5p deletion with hemifacial microsomia and absence of cri-du-chat syndrome

“…Exceptions, however, did occur, but these patients with atypical phenotype were rarely described. These patients had either a small distal deletion at 5p15.3 or an interstitial deletions of 5p15-p14 (Church et al, 1995;Cornish et al, 1999;Kondoh et al, 2005;Hodge et al, 2007). Only one patient with a large distal deletion at 5p13 was reported to have an unusual clinical feature (Azman et al, 2008).…”

Multiplex ligation-dependent probe amplification and array comparative genomic hybridization analyses for prenatal diagnosis of cytogenomic abnormalities

“…This is a submicroscopic deletion undetectable by routine chromosome analysis. The TERT gene has been reported as a candidate gene for Cri du Chat syndrome (OMIM#123450); the most important clinical features are a high-pitched cat-like cry, distinct facial dysmorphism, microcephaly, severe psychomotor and mental retardation [ 20 , 21 ]. However, the normal prenatal ultrasound finding and appear normal development at age of two years in case 5 may represent a mild phenotype.…”