PMC5788284_01
Phenotypic manifestations of our patients, pedigree and electropherograms showing LIPE mutations. A: Lateral view of the head and neck of the patient MSL 36.3 showing marked increase in facial, submental and dorsocervical fat. B: Lateral view of the lower extremities of the patient MSL 36.3 showing loss of subcutaneous fat from the calves and loss of muscle mass. C: Photomicrograph of the deltoid muscle biopsy of MSL 36.3 showing atrophic muscle fibers and regenerating basophilic skeletal muscle cells surrounded by fibrosis. D: T-1 weighted midline sagittal magnetic resonance image of the head and neck of MSL 36.3 showing excess fat accumulation in the anterior and posterior neck region, which measured 6 cm at the paravertebral muscle at the level of cervical five vertebra. E: T-1 weighted axial magnetic resonance image of the neck of MSL 36.3 showing excess fat accumulation in the posterior neck region as well as in the anterior neck. F: T-1 weighted midline axial magnetic resonance image of the upper chest of MSL 36.3 showing excess fat accumulation in the posterior region. G: Anterior view of the patient MSL 36.4 showing marked excess fat accumulation in the anterior neck, upper arms, chest and abdomen. H: Anterior view of the patient MSL 36.4 showing excess fat accumulation in the lower abdomen, pubic and inguinal region. I: MSL 36 Pedigree with consanguinity among parents. Filled symbols indicate affected subjects and unfilled symbols unaffected subjects. The genotypes are indicated under the symbols: G/G wild-type; G/T heterozygotes; T/T homozygotes. Circles denote females and squares denote males. Black color in symbols indicates presence of myopathy; green color, vitiligo; yellow color multiple symmetric lipomatosis (MSL) phenotype; and purple, lipodystrophy of the lower extremities. J: Electropherograms of the part of exon 10 of LIPE showing normal sequence, heterozygous and homozygous c.3013G>T mutation resulting in stop codon at position 1,035 instead of glutamic acid residue. [Color figure can be viewed at wileyonlinelibrary.com].
nihms914758f1.jpg
PMC5788284_03_nihms914758f1.jpg
F1
Given the parental consanguinity (Fig. 1I), we hypothesized that a homozygous mutation shared by the two affected subjects was most likely and therefore filtered for rare missense, nonsense, splicing or frameshift variants with minor allele frequency (MAF) <0.1% in the 1000 Genomes Project and Exome Aggregation Consortium (ExAC) database and GERP++ score >2.0.
PMC5788284_02
Phenotypic manifestations of our patients, pedigree and electropherograms showing LIPE mutations. A: Lateral view of the head and neck of the patient MSL 36.3 showing marked increase in facial, submental and dorsocervical fat. B: Lateral view of the lower extremities of the patient MSL 36.3 showing loss of subcutaneous fat from the calves and loss of muscle mass. C: Photomicrograph of the deltoid muscle biopsy of MSL 36.3 showing atrophic muscle fibers and regenerating basophilic skeletal muscle cells surrounded by fibrosis. D: T-1 weighted midline sagittal magnetic resonance image of the head and neck of MSL 36.3 showing excess fat accumulation in the anterior and posterior neck region, which measured 6 cm at the paravertebral muscle at the level of cervical five vertebra. E: T-1 weighted axial magnetic resonance image of the neck of MSL 36.3 showing excess fat accumulation in the posterior neck region as well as in the anterior neck. F: T-1 weighted midline axial magnetic resonance image of the upper chest of MSL 36.3 showing excess fat accumulation in the posterior region. G: Anterior view of the patient MSL 36.4 showing marked excess fat accumulation in the anterior neck, upper arms, chest and abdomen. H: Anterior view of the patient MSL 36.4 showing excess fat accumulation in the lower abdomen, pubic and inguinal region. I: MSL 36 Pedigree with consanguinity among parents. Filled symbols indicate affected subjects and unfilled symbols unaffected subjects. The genotypes are indicated under the symbols: G/G wild-type; G/T heterozygotes; T/T homozygotes. Circles denote females and squares denote males. Black color in symbols indicates presence of myopathy; green color, vitiligo; yellow color multiple symmetric lipomatosis (MSL) phenotype; and purple, lipodystrophy of the lower extremities. J: Electropherograms of the part of exon 10 of LIPE showing normal sequence, heterozygous and homozygous c.3013G>T mutation resulting in stop codon at position 1,035 instead of glutamic acid residue. [Color figure can be viewed at wileyonlinelibrary.com].
nihms914758f1.jpg
PMC5788284_03_nihms914758f1.jpg
F1
Given the parental consanguinity (Fig. 1I), we hypothesized that a homozygous mutation shared by the two affected subjects was most likely and therefore filtered for rare missense, nonsense, splicing or frameshift variants with minor allele frequency (MAF) <0.1% in the 1000 Genomes Project and Exome Aggregation Consortium (ExAC) database and GERP++ score >2.0.
PMC5788284_03
Phenotypic manifestations of our patients, pedigree and electropherograms showing LIPE mutations. A: Lateral view of the head and neck of the patient MSL 36.3 showing marked increase in facial, submental and dorsocervical fat. B: Lateral view of the lower extremities of the patient MSL 36.3 showing loss of subcutaneous fat from the calves and loss of muscle mass. C: Photomicrograph of the deltoid muscle biopsy of MSL 36.3 showing atrophic muscle fibers and regenerating basophilic skeletal muscle cells surrounded by fibrosis. D: T-1 weighted midline sagittal magnetic resonance image of the head and neck of MSL 36.3 showing excess fat accumulation in the anterior and posterior neck region, which measured 6 cm at the paravertebral muscle at the level of cervical five vertebra. E: T-1 weighted axial magnetic resonance image of the neck of MSL 36.3 showing excess fat accumulation in the posterior neck region as well as in the anterior neck. F: T-1 weighted midline axial magnetic resonance image of the upper chest of MSL 36.3 showing excess fat accumulation in the posterior region. G: Anterior view of the patient MSL 36.4 showing marked excess fat accumulation in the anterior neck, upper arms, chest and abdomen. H: Anterior view of the patient MSL 36.4 showing excess fat accumulation in the lower abdomen, pubic and inguinal region. I: MSL 36 Pedigree with consanguinity among parents. Filled symbols indicate affected subjects and unfilled symbols unaffected subjects. The genotypes are indicated under the symbols: G/G wild-type; G/T heterozygotes; T/T homozygotes. Circles denote females and squares denote males. Black color in symbols indicates presence of myopathy; green color, vitiligo; yellow color multiple symmetric lipomatosis (MSL) phenotype; and purple, lipodystrophy of the lower extremities. J: Electropherograms of the part of exon 10 of LIPE showing normal sequence, heterozygous and homozygous c.3013G>T mutation resulting in stop codon at position 1,035 instead of glutamic acid residue. [Color figure can be viewed at wileyonlinelibrary.com].
nihms914758f1.jpg
PMC5788284_03_nihms914758f1.jpg
F1
Given the parental consanguinity (Fig. 1I), we hypothesized that a homozygous mutation shared by the two affected subjects was most likely and therefore filtered for rare missense, nonsense, splicing or frameshift variants with minor allele frequency (MAF) <0.1% in the 1000 Genomes Project and Exome Aggregation Consortium (ExAC) database and GERP++ score >2.0.