Refined genotype–phenotype correlations in cases of chromosome 6p deletion syndromes

Abstract

Clinical reports of cases with deletions in chromosome 6p are relatively rare. We present a detailed study by fluorescent in situ hybridisation (FISH) of six new cases with distinct but overlapping 6p deletions involving the 6p24 -pter chromosomal segment. Chromosomal breakpoints in individual cases were investigated using a large panel of probes previously mapped and characterised in our laboratory to cover the distal region of 6p. These cases have allowed refinement of genotype -phenotype correlations and strongly suggest a gene involved in regulating the development of hearing is localised within 6p25. There is also evidence for one or more loci involved in heart, skeletal and craniofacial development in the 6p24-p25 region. Furthermore, the Dandy -Walker malformation is associated with deletion of 6p24 -pter.

Schizophrenia in an adult with 6p25 deletion syndrome

“…Table II presents a summary of this patient in the context of previous reports of adults and adolescents with distal 6p deletions [Jalal et al, 1989;Palmer et al, 1991;Law et al, 1998;Davies et al, 1999b;Le Caignec et al, 2005]. The patient presented in this report has many typical features of 6p25 deletion syndrome, and appears to have greatest similarity to patient SG in Law et al, 1998 and patient 3 in Mirza et al, 2004, with respect to the phenotype and extent of deletion [Law et al, 1998;Mirza et al, 2004]. A normal karyotype in infancy, normal vision, few other health problems and lack of genetics followup likely contributed to lack of recognition of a diagnosable syndrome until she was specifically assessed as an adult.…”

“…Testing of available family members (mother and sister) showed normal chromosomes. Molecular cytogenetic studies using FISH and 6p probes described elsewhere [Davies et al, 1999b;Mirza et al, 2004], with the addition of clones DJ470L22 and DJ69L16 selected from the Ensembl database (http://www.ensembl.org/Homo_sapiens/contingview?mapfrag=RP3-470L22; http:// www.ensembl.orgHomo_sapiens/contingview?mapfrag=RP11-69L16), were used to refine the breakpoint. The research FISH analysis (Fig.…”

PITX2 and FOXC1 spectrum of mutations in ocular syndromes

“…De Hauwere syndrome (OMIM: 109120), characterized by anterior segment eye defects, hypertelorism, psychomotor retardation, hypotonia, hearing loss, hydrocephalus/enlarged ventricles, and femoral head anomalies, 21,22 displays a significant overlap with 6p25 deletion syndrome (OMIM: 612582), defined as a combination of ocular anomalies (primarily anterior segment), hearing loss, congenital heart disease, hydrocephalus, developmental delay, and a characteristic facial appearance and typically associated with terminal deletions of 6p25. 32,33 Review of the literature identified that the skeletal features observed in De Hauwere syndrome, such as flattening of the femoral epiphyses and other femoral head anomalies sometimes diagnosed as Perthes disease, were reported in several previously described patients with 6p25 terminal deletions (Table 3), 32,[34][35][36][37][38] suggesting that De Hauwere syndrome may be part of the 6p25 deletion syndrome spectrum. Case 28 in our study has the smallest and first interstitial deletion reported to date in association with the features of De Hauwere syndrome, thus defining a minimal deleted region for this phenotype.…”

The 6p25 deletion syndrome: An update on a rare neurocristopathy

“…The presence of ASD is reported in 83% of 6p25 deletion syndrome patients (present in 49 out of 59 reported cases, see Table 1). 10,11,[13][14][15][27][28][29][30][31][32][33][34][35] Iris coloboma has been reported in few patients with isolated 6p25 deletion. 14,31 Glaucoma is a common finding, present in about half of patients.…”