Limits...
Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?

Kruszka P, Uwineza A, Mutesa L, Martinez AF, Abe Y, Zackai EH, Ganetzky R, Chung B, Stevenson RE, Adelstein RS, Ma X, Mullikin JC, Hong SK, Muenke M - Mol Genet Genomic Med (2015)

Bottom Line: Using whole exome sequencing, a de novo heterozygous mutation was found in the gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual with LBWC.Human wild-type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA did not, but worsened the phenotype of the morpholino knockdown zebrafish.This study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.

ABSTRACT
Limb body wall complex (LBWC) and amniotic band sequence (ABS) are multiple congenital anomaly conditions with craniofacial, limb, and ventral wall defects. LBWC and ABS are considered separate entities by some, and a continuum of severity of the same condition by others. The etiology of LBWC/ABS remains unknown and multiple hypotheses have been proposed. One individual with features of LBWC and his unaffected parents were whole exome sequenced and Sanger sequenced as confirmation of the mutation. Functional studies were conducted using morpholino knockdown studies followed by human mRNA rescue experiments. Using whole exome sequencing, a de novo heterozygous mutation was found in the gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual with LBWC. Morpholino knockdown of iqck mRNA in the zebrafish showed ventral defects including failure of ventral fin to develop and cardiac edema. Human wild-type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA did not, but worsened the phenotype of the morpholino knockdown zebrafish. This study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.

No MeSH data available.


Related in: MedlinePlus

(A) Frontal view showing ventral midline defect; (B) postnatally acquired skin lesions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585450&req=5

fig01: (A) Frontal view showing ventral midline defect; (B) postnatally acquired skin lesions.

Mentions: Patient 1 is the fourth born of six children from healthy parents. There were no birth complications, and no noted amniotic bands. The patient possessed multiple congenital anomalies (Figs.4) including a 2 cm skin pedicle on his scalp, hypertelorism, depressed nasal bridge, broad nasal root, right cleft lip, large ventral wall defect, spina bifida occulta, and multiple limb anomalies. The ventral wall defect was skin, and not amnion covered. The limb anomalies consisted of right hand amputation-like defect of the 4th and 5th digits at the proximal phalanx (Figs.3B and C, 4A), cutaneous syndactyly of the 2nd and third digit of the left hand (Figs.3C and D, 4B), left congenital talipes equinovarus (Figs.3E, 4C), and bilateral split feet (Figs.3C, 4C and D). The patient had constriction rings on his left forearm and left great toe (Fig.3E and F). Multiple skin lesions were present on his back (Fig.1B), but these were acquired postnatally. An abdominal CT further clarified the anatomy of the ventral wall defect, which showed the right ventricle and part of the left ventricle outside the thoracic cavity and a diastasis of the abdominal musculature with colon protrusion. No diaphragmatic hernia or disruption was found. The sternum, scapula, ribs, liver, spleen, pancreas, adrenals, kidneys, and small bowel were normal. An echocardiogram of the heart showed an atrial septal defect (ASD) and a ventricular septal defect (VSD).


Limb body wall complex, amniotic band sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)?

Kruszka P, Uwineza A, Mutesa L, Martinez AF, Abe Y, Zackai EH, Ganetzky R, Chung B, Stevenson RE, Adelstein RS, Ma X, Mullikin JC, Hong SK, Muenke M - Mol Genet Genomic Med (2015)

(A) Frontal view showing ventral midline defect; (B) postnatally acquired skin lesions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585450&req=5

fig01: (A) Frontal view showing ventral midline defect; (B) postnatally acquired skin lesions.
Mentions: Patient 1 is the fourth born of six children from healthy parents. There were no birth complications, and no noted amniotic bands. The patient possessed multiple congenital anomalies (Figs.4) including a 2 cm skin pedicle on his scalp, hypertelorism, depressed nasal bridge, broad nasal root, right cleft lip, large ventral wall defect, spina bifida occulta, and multiple limb anomalies. The ventral wall defect was skin, and not amnion covered. The limb anomalies consisted of right hand amputation-like defect of the 4th and 5th digits at the proximal phalanx (Figs.3B and C, 4A), cutaneous syndactyly of the 2nd and third digit of the left hand (Figs.3C and D, 4B), left congenital talipes equinovarus (Figs.3E, 4C), and bilateral split feet (Figs.3C, 4C and D). The patient had constriction rings on his left forearm and left great toe (Fig.3E and F). Multiple skin lesions were present on his back (Fig.1B), but these were acquired postnatally. An abdominal CT further clarified the anatomy of the ventral wall defect, which showed the right ventricle and part of the left ventricle outside the thoracic cavity and a diastasis of the abdominal musculature with colon protrusion. No diaphragmatic hernia or disruption was found. The sternum, scapula, ribs, liver, spleen, pancreas, adrenals, kidneys, and small bowel were normal. An echocardiogram of the heart showed an atrial septal defect (ASD) and a ventricular septal defect (VSD).

Bottom Line: Using whole exome sequencing, a de novo heterozygous mutation was found in the gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual with LBWC.Human wild-type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA did not, but worsened the phenotype of the morpholino knockdown zebrafish.This study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.

ABSTRACT
Limb body wall complex (LBWC) and amniotic band sequence (ABS) are multiple congenital anomaly conditions with craniofacial, limb, and ventral wall defects. LBWC and ABS are considered separate entities by some, and a continuum of severity of the same condition by others. The etiology of LBWC/ABS remains unknown and multiple hypotheses have been proposed. One individual with features of LBWC and his unaffected parents were whole exome sequenced and Sanger sequenced as confirmation of the mutation. Functional studies were conducted using morpholino knockdown studies followed by human mRNA rescue experiments. Using whole exome sequencing, a de novo heterozygous mutation was found in the gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual with LBWC. Morpholino knockdown of iqck mRNA in the zebrafish showed ventral defects including failure of ventral fin to develop and cardiac edema. Human wild-type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA did not, but worsened the phenotype of the morpholino knockdown zebrafish. This study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.

No MeSH data available.


Related in: MedlinePlus