HOXA2 Haploinsufficiency in Dominant Bilateral Microtia and Hearing Loss

被引：44

作者：

Brown, Kerry K. ^{[1
,2
]}

Viana, Lucas M. ^{[1
,3
,4
]}

Helwig, Cecilia C. ^{[5
]}

Artunduaga, Maria A. ^{[6
]}

Quintanilla-Dieck, Lourdes ^{[7
]}

Jarrin, Patricia ^{[8
]}

Osorno, Gabriel ^{[9
]}

McDonough, Barbara ^{[1
,2
]}

DePalma, Steven R. ^{[1
,10
]}

Eavey, Roland D. ^{[11
]}

Seidman, Jonathan G. ^{[1
]}

Seidman, Christine E. ^{[1
,2
,10
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA

[3] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA

[4] Univ Brasilia, Fac Hlth Sci, Brasilia, DF, Brazil

[5] Geisinger Med Ctr, Dept Pediat Otolaryngol, Danville, PA 17822 USA

[6] Univ Chicago, Med Ctr, Dept Surg, Sect Plast & Reconstruct Surg, Chicago, IL 60637 USA

[7] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA

[8] Hosp Un Canto Vida, Fdn Tierra Nueva, Quito, Ecuador

[9] Univ Nacl Colombia, Fac Med, Unidad Cirugia Plast, Bogota, Colombia

[10] Howard Hughes Med Inst, Chevy Chase, MD USA

[11] Vanderbilt Univ, Med Ctr, Dept Otolaryngol, Vanderbilt Bill Wilkerson Ctr, Nashville, TN 37232 USA

来源：

HUMAN MUTATION | 2013年 / 34卷 / 10期

关键词：

microtia; hearing loss; exome sequencing; HOXA2; HOMEOTIC TRANSFORMATION; MUTATION;

D O I：

10.1002/humu.22367

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Microtia is a rare, congenital malformation of the external ear that in some cases has a genetic etiology. We ascertained a three-generation family with bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing of affected family members detected only seven shared, rare, heterozygous, nonsynonymous variants, including one protein truncating variant, a HOXA2 nonsense change (c.703C>T, p.Q235*). The HOXA2 variant was segregated with microtia and hearing loss in the family and was not seen in 6,500 individuals sequenced by the NHLBI Exome Sequencing Project or in 218 control individuals sequenced in this study. HOXA2 has been shown to be critical for outer and middle ear development through mouse models and has previously been associated with autosomal recessive bilateral microtia. Our data extend these conclusions and define HOXA2 haploinsufficiency as the first genetic cause for autosomal-dominant nonsyndromic microtia. (C) 2013 Wiley Periodicals, Inc.

引用

页码：1347 / 1351

页数：5

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