EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndromeReportar como inadecuado

EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 16:23

Clinical-Molecular Genetics and Cytogenetics


BackgroundWaardenburg syndrome type I WS1, an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1.

Case presentationWe reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature 83.5 cm −5.8SD. His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 IGF-1 was 52.7 ng-ml, lower than the normal range 55 ~ 452 ng-ml and the peak growth hormone level was 7.57 ng-ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone rhGH replacement therapy, showing a 9.2 cm-year growth rate and an improvement of 1 standard deviation SD of height after one year treatment. CMA test of patient’s DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 hg19; chr2:221,234,146-225,697,363.

ConclusionsPAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.

KeywordsChromosomal microarray 2q35-q36.2 PAX3 Waardenburg syndrome EPHA4 Short stature AbbreviationsPAX3Paired box 3

WSWaardenburg syndrome

CMAChromosomal microarray

EPHA4Ephrin Receptor A type 4

SDStandard deviation

TSHThyroid stimulating hormone

FT3Free triiodothyronine

FT4Free thyroxine

FSHFollicle stimulating hormone

LHLuteinizing hormone

IGF-1Insulin-like growth factor-1

MRIMagnetic resonance imaging

rhGHRecombinant human growth hormone


GHRGrowth hormone receptor

JAK2Janus kinase 2

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Autor: Chuan Li - Rongyu Chen - Xin Fan - Jingsi Luo - Jiale Qian - Jin Wang - Bobo Xie - Yiping Shen - Shaoke Chen

Fuente: https://link.springer.com/

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