Patient 1 DNA was isolated from a cell line supplied from Coriell Institute For Medical Research Cell Repository (#GMO6222). For all other patients, DNA was extracted from peripheral blood leukocytes [24
] collected in EDTA tubes after informed written consent was obtained. To determine the number of alleles for polymorphic loci, 35
S-dATP was directly incorporated into PCR products. The PCR products were then separated on 6% polyacrylamide gels. Patients were considered to be heterozygous for a locus when two alleles were observed, and homozygous/hemizygous for a locus when only one allele was observed. To maximize the chances of detecting heterozygosity for a particular marker, markers with heterozygosity in excess of 75% were chosen with the exception of D6S942 and D6S1006, which have heterozygosity of approximately 50% and 61% respectively. Marker information can be obtained from http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?db=unists
Clinical reports for each patient were obtained from the physician who referred the patient. To be thorough, in addition to reporting phenotypes observed, we also reported when a specific phenotype was looked for but not observed. The number of patients in the literature with the same clinical phenotypes are indicated in Table . Table is a summary of the patients for whom molecular characterizations of the deletion have been determined.
Clinical features of deletion patients in this study and a survey of the literature.
Clinical features of patients with characterized terminal deletions.
Patient 1 – 46, XX, del(6)(p24)
Patient 1 sample and clinical details were obtained from Coriell Institute For Medical Research Cell Repository (#GMO6222). The patient had Dandy-Walker cyst, hydrocephalus, Peters' anomaly, hypertelorism, ear tags, low set ears, and normal Hageman factor level in blood.
Patient 2 – 46, XY, del(6)(p24)
Patient 2 had bilateral microphthalmia, corneal opacities, interstitial keratitis and nystagmus. Craniofacial malformations included microcephaly, hypertelorism, low set, posteriorly angulated ears, and a high arched palate. The patient had severe, progressive, congenital scoliosis and profound bilateral clubfoot. An examination of the chest revealed widely spaced nipples. An x-ray was conducted but was unremarkable. Cardiac findings included a grade II to grade III murmur, a patent ductus arteriosus (PDA), a patent foramen ovale (PFO), right ventricular hypertrophy and left axis deviation. There was no ventricular septal defect (VSD) and the PFO closed with time. Hydrocephalus was noted at birth and a brain MRI revealed Dandy-Walker variant. The corpus callosum was thin and upwardly bowed and the middle and inferior portions of the cerebellar vermis were absent. The patient had severe hearing impairment. Genitourinary malformations included micropenis and hydronephrosis secondary to left ureteropelvic junction obstruction. The patient has a history of chronic oliguria, and chronic neutropenia. Results of liver and renal function tests were normal.
Patient 3 – 46, XY, del(6)(p24)
Patient 3 had slanted palpebral fissures, shallow orbits, bilateral hyperopia, Rieger malformation, hypoplastic irides, mild megalocornea, sclerocornea, and bilateral crescentic hyperpigmentation of the retina. The lenses were clear and the intraocular pressures (IOP) were normal. There was no nystagmus or strabismus and the optic nerve head, macula and vessels appeared normal. Craniofacial malformations included hypertelorism, brachycephaly, flat mid-face, low-set ears, small nose, broad nasal bridge, frontal bossing, and mild micrognathia. The patient also had a short neck, scoliosis, proximately flexed thumbs, club feet, and mild clinodactyly of the 5th fingers. His nipples were widely spaced and there were five supernumerary nipples. At birth he had a PFO, a VSD, and tricuspid valve regurgitation; however, all three resolved by the age of one year without intervention. Dandy Walker variant, agenesis of the corpus callosum and brainstem, seizures and profound bilateral deafness were all present. His knees were normal and hips were stable in all ranges of motion but there was delayed ossification of the femoral and humeral heads. Bone age was consistent with a one-year-old child when the patient was two years of age. Fingernails and toenails were soft and the patient had eczema. Genitalia, liver and spleen were all normal.
Patient 4 – 46, XYder(6)t(4;6)(p14;p25)
Patient 4 had an unbalanced translocation resulting in monosomy for 6p25-ter and trisomy of 4p14-ter. The patient had congenital glaucoma, nystagmus, strabismus and Rieger malformation including posterior embryotoxon, iris adhesions, bilateral elevated IOP and a diffuse corneal opacity on the right eye. This patient had no craniofacial malformations, cardiac murmur, neurological abnormalities, or remarkable abnormalities of the chest, hands and feet or kidneys.
Patient 5 – 46, XY, der(6)t(6;8)(p25;q24.1)
Patient 5 had an unbalanced translocation resulting in monosomy for 6p25-ter and trisomy for 8q24.1-ter. At birth the infant was in the 10th centile for height and weight, was hypotonic and had little spontaneous movement. He had Reiger anomaly including ectropian uveae with adhesions around the entire iridocorneal angle and bilateral congenital glaucoma. The optic nerve head appeared normal. Facial malformations included turricephaly, hypertelorism and low set, anteriorly displaced ears. The patient had kyphoscoliosis, hemivertebrae (T5-T6), and did not have a full complement of ribs. Abdominal ultrasound, shoulders and pelvis were all unremarkable. Nail hypoplasia was observed and the patient had sparse eyebrows and lashes. Cardiac malformations were atrial septal defect (ASD), PDA and PFO. He had mild hydrocephalus and hearing loss, however, the cerebellum was normal and an EEG was unremarkable.
Patient 6 – 46, XX, der(6)t(2;6)(q32;p24)
Patient 6 had an unbalanced translocation resulting in monosomy for 6p24-ter and trisomy for 2q32-ter. She had bilateral aniridia, and a vascularized corneal opacification but IOP was normal in each eye. The left eye was smaller than the right and the right eye had extensive retinal pigment epithelial washout and thinning of the retina. Craniofacial malformations included microdolichocephaly, telecanthus, hypertelorism, low-set ears, a broad nasal bridge, cleft palate, micrognathia, long philtrum, prominent premaxilla and a short neck. She had adducted thumbs and camptodactyly of her hands and a valgus deformity of the left foot. The patient also had limited flexion and extension of elbows, knees, and hips and had asymmetrical hypoplasia of vertebrae T12. As an infant the patient had apneic spells with cyanosis and bradycardia while feeding although the cardiovascular system, chest, and abdomen were unremarkable upon examination. A computed tomography scan of the head was normal. The patient had progressive hearing loss and was fitted for a hearing aid at the age of 7 months. Genitalia were normal but right hydronephrosis and a bilateral cystouretero reflux were documented.
Patient 7 had an unbalanced translocation resulting in monosomy of 6p25-ter and a trisomy of the terminal portion of chromosome 10p. She had hypotonia, mild developmental delay and Rieger anomaly. Craniofacial malformations included hypertelorism, a flat nasal bridge, small, low set ears, micrognathia, prognathia and a small mouth with protruding tongue. The patient had scoliosis, a short neck, widespread nipples and malformation of both hands. There was no heart murmur, neurological malformations or hearing impairment.