Limits...
Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array.

Tamura M, Isojima T, Kawashima M, Yoshida H, Yamamoto K, Kitaoka T, Namba N, Oka A, Ozono K, Tokunaga K, Kitanaka S - PLoS ONE (2015)

Bottom Line: She was successfully treated with high-dose oral calcium.Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders.Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

ABSTRACT

Context: Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR) gene. No patients have been reported with uniparental disomy (UPD).

Objective: Using genome-wide single nucleotide polymorphism (SNP) array to confirm whether HVDRR was caused by UPD of chromosome 12.

Materials and methods: A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array.

Results: The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father's allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents) showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium.

Conclusions: This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

No MeSH data available.


Related in: MedlinePlus

Alopecia and Rickets in the Proband at Presentation.(A) Alopecia. (B,C) A bone roentgenogram of the arm (B) and legs (C) showing cupping, fraying, and flaring at the end of the long bones.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496068&req=5

pone.0131157.g001: Alopecia and Rickets in the Proband at Presentation.(A) Alopecia. (B,C) A bone roentgenogram of the arm (B) and legs (C) showing cupping, fraying, and flaring at the end of the long bones.

Mentions: A 2-year 1-month-old girl presented to hospital with fever, at which point she was noted to have short stature, alopecia (Fig 1), and gait instability. Her parents were non-consanguineous and approximately 30 years old when she was born. She had no family history of rickets or unresolved pain. Her mother got a natural conception, and the pregnancy and delivery was uneventful. Her birth weight was 2,868 g (-0.8 standard deviations [SD]), birth length 51 cm (+0.6 SD), gestational age 41 weeks. She had no episode of convulsion and her psychomotor development was normal until she started walking alone at 1 year 3 months of age, but she could not run by age 2. Her body height at presentation was 74.8 cm (−3.5 SD), and her body weight, 9.7 kg (−1.2 SD). She had symptoms of rickets such as bow-legs and enlargement of the limb joints, but had no other external malformation, dysmorphic features, or ataxia. Her verbal developmental quotient (DQ) was 81 and cognitive DQ 94.


Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array.

Tamura M, Isojima T, Kawashima M, Yoshida H, Yamamoto K, Kitaoka T, Namba N, Oka A, Ozono K, Tokunaga K, Kitanaka S - PLoS ONE (2015)

Alopecia and Rickets in the Proband at Presentation.(A) Alopecia. (B,C) A bone roentgenogram of the arm (B) and legs (C) showing cupping, fraying, and flaring at the end of the long bones.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496068&req=5

pone.0131157.g001: Alopecia and Rickets in the Proband at Presentation.(A) Alopecia. (B,C) A bone roentgenogram of the arm (B) and legs (C) showing cupping, fraying, and flaring at the end of the long bones.
Mentions: A 2-year 1-month-old girl presented to hospital with fever, at which point she was noted to have short stature, alopecia (Fig 1), and gait instability. Her parents were non-consanguineous and approximately 30 years old when she was born. She had no family history of rickets or unresolved pain. Her mother got a natural conception, and the pregnancy and delivery was uneventful. Her birth weight was 2,868 g (-0.8 standard deviations [SD]), birth length 51 cm (+0.6 SD), gestational age 41 weeks. She had no episode of convulsion and her psychomotor development was normal until she started walking alone at 1 year 3 months of age, but she could not run by age 2. Her body height at presentation was 74.8 cm (−3.5 SD), and her body weight, 9.7 kg (−1.2 SD). She had symptoms of rickets such as bow-legs and enlargement of the limb joints, but had no other external malformation, dysmorphic features, or ataxia. Her verbal developmental quotient (DQ) was 81 and cognitive DQ 94.

Bottom Line: She was successfully treated with high-dose oral calcium.Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders.Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

ABSTRACT

Context: Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR) gene. No patients have been reported with uniparental disomy (UPD).

Objective: Using genome-wide single nucleotide polymorphism (SNP) array to confirm whether HVDRR was caused by UPD of chromosome 12.

Materials and methods: A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array.

Results: The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father's allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents) showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium.

Conclusions: This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

No MeSH data available.


Related in: MedlinePlus