We report molecular genetic analysis of 42 affected individuals referred with a diagnosis of aniridia who previously screened as negative for intragenic PAX6 mutations. Of these 42, the diagnoses were 31 individuals with aniridia and 11 individuals referred with a diagnosis of Gillespie syndrome (iris hypoplasia, ataxia and mild to moderate developmental delay). Array-based comparative genomic hybridization identified six whole gene deletions: four encompassing PAX6 and two encompassing FOXC1. Six deletions with plausible cis-regulatory effects were identified: five that were 3ʹ (telomeric) to PAX6 and one within a gene desert 5ʹ (telomeric) to PITX2. Sequence analysis of the FOXC1 and PITX2 coding regions identified two plausibly pathogenic de novo FOXC1 missense mutations (p.Pro79Thr and p.Leu101Pro). No intragenic mutations were detected in PITX2. FISH mapping in an individual with Gillespie-like syndrome with an apparently balanced X;11 reciprocal translocation revealed disruption of a gene at each breakpoint: ARHGAP6 on the X chromosome and PHF21A on chromosome 11. In the other individuals with Gillespie syndrome no mutations were identified in either of these genes, or in HCCS which lies close to the Xp breakpoint. Disruption of PHF21A has previously been implicated in the causation of intellectual disability (but not aniridia). Plausibly causative mutations were identified in 15 out of 42 individuals (12/32 aniridia; 3/11 Gillespie syndrome). Fourteen of these mutations presented in the known aniridia genes; PAX6, FOXC1 and PITX2. The large number of individuals in the cohort with no mutation identified suggests greater locus heterogeneity may exist in both isolated and syndromic aniridia than was previously appreciated.
The proband, first of the twins, weighed 2430 g (> 10th centile), the co-twin weighing 2130 g (<10th centile). The most striking features on examination of the proband were macroglossia, moderate sized exomphalos, and widely spaced nipples. No indentation of the ear lobules was noted. Early hypoglycaemia was managed with dextrose infusion, and the exomphalos was corrected within the first 24 hours of life. The second twin was of normal appearance but was small for gestational age. There were no neonatal problems. Examination of the parents did not reveal any ear creases, posterior pits, or divarication of rectus muscles, and they were not of large birthweight.After initial catch up growth the second twin's growth variables at the age of 18 months continued along the 10th centile, and developmental assessment at that age was within normal limits. The proband had feeding difficulties related to her macroglossia, and partial glossectomy was eventually performed at the age of 17 months. Despite these problems her growth has continued along the 50th centile for height, weight, and occipitofrontal head circumference. At the age of 18 months her development was delayed by six months. No abdominal mass was detected at any time.Investigations to determine zygosity showed both twins to be of blood groups A, rr. They were identical when typed for Kell, Fya, Jka, P1, and MNS. In the HLA system both were A 3, 30, B7, 13, and CW 7. The parents were also typed and the final probability of monozygosity was 0 995. Chromosomal preparations were made from cells cultured from peripheral blood of both twins and stained to reveal both C and G bands. No differences were observed in C band polymorphisms, thus supporting monozygosity, and no abnormality was detectable on any chromosome of either child. Chromosome 11 was particularly closely examined on prometaphase cells. Discussion
If you have a burning desire to respond to a paper published in ADC or F&N, why not make use of our "rapid response" option? Log on to our website (www. archdischild.com), find the paper that interests you, click on "full text" and send your response by email by clicking on "submit a response". Providing it isn't libellous or obscene, it will be posted within seven days. You can retrieve it by clicking on "read rapid responses" on our homepage.
'Facial naevus flammeus with choroidal haemangioma and without intracranial involvement' SIR-We would like to report a male patient who was noted at birth to have left-sided facial naevus flammeus (port wine stain) involving the left side of the scalp, upper eyelid, and the left side of the nose. Follow-up in the next 6 years did not show any developmental problems, focal neurological deficit, nor seizures. His left eye was found to be hyperaemic over the bulbar conjunctiva. He also had anisometropic hyperoptic astigmatism of the left eye. Fundal examination confirmed the presence of left choroidal haemangioma, mainly in the upper half and posterior pole of the choroid. It was a well circumscribed lesion, slightly raised, bright red in colour, and affecting the left foveal region. The child had no evidence of raised intraocular pressure. The latest follow-up assessment at 6 years recorded visual acuity of 6/5(right eye) and 6/9 (left eye) with glasses correction. He is currently undergoing treatment for left amblyopia.At 18 months of age the child had brain CT which was normal. To clarify the diagnosis further, and to be in a position to give the parents an accurate diagnosis and prognosis, MRI was performed at the age of 6 years. Brain imaging enhanced by gadalinium -DTPA was performed. This showed diffuse enhancement of the choroid with choroidal angioma of the left eye. There was no intracranial abnormality.Naevus flammeus can be an isolated birthmark or it can be associated with ophthalmological and/or neurological abnormalities. When neurological abnormalities are present the diagnosis of Sturge-Weber syndrome (SWS) is highly likely. Stevenson and colleagues reported ocular findings in 50 patients with naevus flammeus. 1,2 Only one patient was found to have clinical evidence of choroidal haemangioma and this patient did not have intracranial abnormalities. Sullivan and coworkers reported the ocular manifestations of SWS in 51 patients. Of these, 28 had choroidal haemangiomas. 3 Choroidal haemangiomas in SWS patients are usually diffuse, primarily related to the posterior pole, and usually seen as red, flat to moderately elevated masses. This is in contrast to choroidal haemangiomas not associated with SWS which are usually discreet raised structures arising from the choroid. 4 In our patient, the naevus flammeus involves the ophthalmic and maxillary divisions of the trigeminal nerve and the choroidal haemangioma has the characteristics of those seen in SWS. However, the child does not have any neurological deficit.We feel it is appropriate in these cases to clarify the possibility of intracranial involvement with neuroimaging to be able to give parents an accurate prognosis. 'Salivary cortisol in children with cognitive impairment' SIR-Cortisol plays an essential role in stress-regulation in humans. 1 It is produced in a well-defined circadian rhythm which is under the influence of an individual's sleep-wake activity. Under basal conditions, cortisol levels are highest in the early morning and subsequent...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.